Does cartilage connect to other cartilage?

Does cartilage connect to other cartilage?

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In the definition of a Ligament in Oxford states:

A short band of tough, flexible fibrous connective tissue which connects two bones or cartilages or holds together a joint.

the wording of "two" prior to bones or cartilages sounds like it could be bone to bone, cartilage to cartilage, and bone to cartilage.

Are all of these combinations correct? If so, is there a good example where each one can be seen for reference?

A ligament can connect two bones:

Picture 1: Knee joint ligaments (source: Wikipedia, Creative Commons license)

A ligament can connect two cartilages or a bone and a cartilage:

Picture 2: Larynx ligaments (source: Wikipedia, Creative Commons license)

Ligaments can also connect internal organs:

Picture 3: Ligaments connecting abdominal organs (source: Wikipedia, Creative Commons license)

Humans May Possess Ability to Regrow Cartilage

WEDNESDAY, Oct. 9, 2019 (HealthDay News) -- Humans may lack the salamander skill of regrowing a limb, but a new study suggests they do have some capacity to restore cartilage in their joints.

The findings run counter to a widely held belief: Because the cartilage cushioning your joints lacks its own blood supply, your body can't repair damage from an injury or the wear-and-tear of aging.

And that, in part, is why so many people eventually develop osteoarthritis, where broken-down cartilage causes pain and stiffness in the joints.

But that lack of blood supply does not mean there's no regenerative capacity in the cartilage, according to Dr. Virginia Byers Kraus, the senior researcher on the new study.

In fact, her team found evidence that human cartilage can, to some degree, renew itself, using a molecular process similar to the one that allows a salamander to grow a new limb.

The researchers are calling it the "inner salamander capacity."

"For the first time, we have evidence that the joint has the capacity to repair itself," said Kraus, a professor at Duke University School of Medicine, in Durham, N.C.

Specifically, she explained, that capability exists in a "gradient." It's greatest in the ankle, less apparent in the knee, and lowest in the hip.

And that makes sense if this repair capability is an artifact of evolution, according to Kraus. Animals that regenerate tissue have the greatest capacity for it in the distal portions of the body -- the parts "most likely to get chewed off."

Dr. Scott Rodeo, an orthopedic surgeon not involved in the study, said the findings raise some interesting questions.

For one, he said, could this be a partial explanation for why osteoarthritis is common in the knees and hips, but not the ankles?

"It's been assumed that it's related to the biomechanics of the joints," said Rodeo, an attending surgeon at the Hospital for Special Surgery, in New York City.

But this study, he said, suggests there might be intrinsic differences in the joints' ability to repair cartilage.

The other major question, Rodeo said, is whether this newfound human capacity can translate into new treatments for arthritis. "Can we better understand the basic biology, and harness it?" he asked.

For the study, Kraus and her colleagues analyzed proteins in samples of joint cartilage that had been removed from patients having surgery. The researchers developed a method for gauging the "age" of those proteins, based on the premise that young proteins have little to no evidence of "conversions" of amino acids (the building blocks of proteins), while older proteins have many conversions.

Overall, the investigators found, ankle cartilage showed the greatest number of young proteins. Knee cartilage looked more middle-aged, and hip cartilage had relatively few young proteins and plenty of old.

In addition, the study found, molecules called microRNAs seem to regulate the process. They were more abundant in ankle cartilage than tissue from knees and hips, and in the top layers of cartilage, versus the deeper layers.

As it happens, microRNAs also help salamanders regrow lost limbs.

The findings were published online Oct. 9 in the journal Science Advances.

It all raises the possibility that the innate repair capacity in cartilage can be augmented, according to Kraus. Could, for example, injectable microRNA drugs be used to boost cartilage self-repair?

No one is saying science is close to helping humans grow new limbs. But, Kraus said, understanding the fundamental mechanisms behind tissue regeneration -- figuring out what salamanders have that people are missing -- could eventually lead to ways to repair various tissues in the human body.

Rodeo agreed. "Can we learn lessons from animals that do regenerate tissue, and apply that to humans?"

Both he and Kraus said there is a "huge" need for innovative ways to treat osteoarthritis, which affects roughly 27 million Americans, according to the Arthritis Foundation. There is no cure, and current treatments are aimed at managing symptoms.

When people are disabled by arthritis, Kraus noted, that can also raise their risk of other major health problems, including type 2 diabetes and heart disease.

Process of Ossification in Human Body | Connective Tissues | Biology

Development of bone begins from mesoderm in the embryonic life (from sixth week) and a good number of bones of the human body continue to grow until a person reaches about twenty-fifth years. There are two processes of ossification-intramembranous and intracartilaginous (endochondral). The bones of the cranial vault and the mandible are membranous in origin. The bones of the limbs, trunk and base of the skull are both cartilaginous and membranous in development.

1. Intramembranous Ossification:

It is the simpler form of ossification and most bones of the face, cranial vault and clavicles are formed in membrane. In this process of ossification the embryonic mesenchymes consisting of the primitive connective tissue become congregated or connected by their processes without having cytoplasm continuity. This area becomes richly vascularised. (Fig. 1.52)

The mesenchymal cells (preosteoblasts) increase in size and are clustered together to form long strands of cells radiating in all directions and secrete collagenous fibrils. The cytoplasms of the mesenchymal cells become basophilic and ultimately differentiated into osteoblasts. Between osteoblasts, their bars (trabeculae) of dense intercellular substance appear and mark the connective tissue fibres (osteogen fibres) already presents within the matrix.

The cells ultimately become embedded by the bars of dense matrix that increase in size. The matrix at this stage is not calcified and the tissue thus formed is loose. Between cells and collagenous fibrils, a semisolid fluid, osseomucoid is present. The organic non-calcified component is known as osteoid.

Later on calcium salts are deposited presumably by the activity of osteoblasts. As the osteoblasts deposit successive layers of calcium salts in the matrix, certain osteoblasts are also entrapped within minute spaces— lacunae. These entrapped osteoblasts are osteocytes. Lacunae and canaliculi are successively formed and can­aliculi of adjoining lacunae thus connect with each other.

Spicules (bars) of bone, containing osteocytes and sur­rounded by actively secreting osteoblasts, can now be rec­ognised. As the bony spicules increase in size and complexity, so the osteoblasts proliferate to keep pace with the require­ment for more bone-forming cells. In this process, cancellous bone forms. All newly formed bones are cancellous (Fig. 1.53) whether produced intramembranously or by intracartilagi- nous ossification.

After this initial stage of bone formation the osteoblast ap­pears on the surface of the newly formed bone and through the activity of the osteoblast the thickness of bone is increased. The source of osteoblast in the surface is maintained through the mitosis and also from the undifferentiated cells in the sur­rounding connective tissue. At the periphery of the ossification centre, the mesenchyme condenses to form the periosteum.

2. Intracartilaginous (Endochondral) Development of Bone:

Through this process most of the skeletal bones are formed. In the embryo, where the bone formation is re­quired, mesenchymal cells become developed into a cartilag­inous model. Ultimately, the cartilage cells completely disap­pear and it is transformed into bone. (Fig. 1.54)

The importance of this provisional cartilaginous foundation lies in three facts:

i. It provides a suitable medium for the deposition of calcium salts.

ii. It serves to determine roughly what shape the finished bone will take in future.

iii. It is by the growth of this cartilage (then known as epiphyseal cartilage) that the bone grows in length.

Process of Intracartilaginous Bone Formation:

In a long bone of a limb the ossification initially starts with the appearance of a fibrous membrane around the centre of cartilage model. This fibrous membrane, perichondrium, has got osteogenic function and cells of the perichondrium adjoining the cartilage become hypertrophied and give off long processes to form a meshwork of interlacing fibres.

These cells are osteoblasts and fibrous network is then impregnated with calcium salt and forms a true bone beneath the perichondrium. This bone provides a rigid mass and surrounds the cartilage as collar or ring which is known as periosteal bone collar or ring or subperiosteal bone. The perichondrium thus afterwards becomes periosteum.

Simultaneously with the formation of collar, certain changes in the centre of shaft (diaphysis) of the car­tilaginous model are observed. This centre is known as primary ossification centre. The cartilage cells become hypertrophied accumulating glycogen and appropriate glycolytic enzyme and phosphatase and throw out longitudinal row of cartilage cells on both sides.

As the cartilage cells are hypertrophied, the intercellular substance is also sufficiently hypertrophied and secretes phosphate. If calcium and phosphates are available around the cartilage spicules (spiky remnants of the cartilage model) in a certain proportion relative to each other (this proportion being controlled to some extent by the activity of ductless glands), then the intercellular substance is calcified. With the calcification, the cartilage cells become cut off from nutrition and cells die.

With the dis­integration of the calcified cartilage at the centre of the cartilaginous model (primary ossification centre), irregular cavities are formed in the cartilage matrix. Periosteal bud consisting of the osteogenic cells (undifferentiated mesenchymal cells of perichondrium), osteoblast and capillaries of the inner layer of periosteum, invades these cavities.

The osteoblasts that are initially advanced into the interior of blood vessels thus lay down bone on the remnants of the cartilage intercellular substance. These spaces of the shaft are joined up to form the Haversian canals which help as conduits for running of blood vessels.

The process of ossification proceeds and extends from the centre of the shaft towards the ends of the cartilage. The periosteal bone collar also becomes thicker and extends towards the epiphyses. This bone collar gives a support in maintaining the strength of the shaft. Besides this the thickness of the bone depends upon the activity of the deeper layer of the periosteum of the shaft.

At somewhat later date, and possibly at the time of birth secondary ossification centres appear in each epiph­ysis of the long bones. The segmental changes for calcification and subsequent ossification are the same as described for the diaphysis. Cartilage cells are hypertrophied and after-wards calcified. The calcified carti­lage is resorbed as usual.

Ossification afterwards is started by the osteoblast on the wall of spaces created due to calcification. Bone deposition is exempted on two regions—particular region and epiphyseal plate. Cartilage cells remain over these areas. The epiphyseal plate or cartilage keeps the diaphysis and epiphysis separated from each other up to certain years of age (app. 25 years) after which the same becomes fused with each oth­er. The growth of the long bone in length depends upon the growth of the epiphyseal plate.

The epiphyseal plate goes on multiplying continuously and throws out longitudinal rows of cartilage cells on both sides. This newly formed cartilage becomes ossified and in this way the bone grows in length. In younger life the rate of multiplication of the epiphyseal cartilage is proportionately more than the rate of calcification. Conse­quently, long bone increases in length.

Growth apparatus is formed by epiphyseal cartilage with metaphysis and is the route of growth in length of long bones. Metaphysis is the column of spongy bones and units of the epiphyseal cartilage to the shaft (diaphysis). But, as age advances the rate of multiplication of cartilage cells slows down, so that the process of calcification becomes relatively more rapid and overtakes the whole strip of the multiplying cartilage. Thus the epiphyseal cartilage becomes ossified and growth in length ceases. Near about the twenty-fifth year of life all the epiphyseal cartilages are ossified and replaced by a spongy bone and marrow.

After fusion of the epiphyseal bone with the diaphysis, the growth in length of the bone becomes quite im­possible and growth is stimulated afterwards by over activity of the growth hormones or somatotrophs hormone (STH) then abnormal growth occurs. This overgrowth of bone is mostly confined to the bones of the face, hands and legs. This condition is known as acromegaly. On the other hand, if this STH is secreted before the fusion of the epiphyseal bone with diaphysis then excess growth of the immature long bone occurs causing gigantism.

Histological changes evolved in endochondral ossification: These changes can be seen in longitudinal sec­tion of a developing long bone of a limb. Three stages are seen during cartilaginous ossification.

1. The stage of hypertrophy (Fig. 1.55).

This is seen in the Primary ossification centre and presents the follow­ing features:

i. The first indication of bone formation is at the perichondrium around the centre of diaphysis. The cells here hypertrophy and become osteoblasts. The osteogenic activity of osteoblasts changes the perichon­drium into a periosteum.

ii. The cartilage cells enlarge and become arranged in linear rows, radiating from the centre.

iii. Irregular deposition of calcium salts takes place between the cells. This part of ossification is of membra­nous development.

2. The stage of irruption (Fig. 1.56). This stage comes a little later than the first stage. The sub-periosteal cells become hyperactive and eat away a portion of the newly formed subperiosteal membrane bone.

Through this eroded spot the periosteal bud containing osteoblasts, osteoclasts, connective tissue and blood vessels stream down into the depth of the bone and invade the calcified mass in the primary ossification centre. The hollow spaces opened up in the process are the primi­tive marrow spaces and their contents are the primitive bone marrow. Even during this early stage red and white blood cells can be seen in various stages of development.

3. The stage of ossification or the stage of true bone forma­tion (Fig. 1.57). This process is similar to intramembra- nous bone formation. Gradually, the marrow spaces in the centre coalesce and from medullary canal. Similarly, Haversian systems are developed.

The bone increases in diameter by two opposite processes going on simultaneously. On the external surface the sub-­periosteal osteoblasts deposit layers of membrane bone, while, in the interior, cells of the endosteum absorb layers of bone from walls of the medullary canal. In this way bone increases in breadth and the medullary canal widens.

It should be noted that the healthy adult bone is not a fixed static material. It is constantly being broken down, re­absorbed and repaired by the co-ordinated activities of os­teoclasts and osteoblasts. Osteoblasts elaborate alkaline phosphatase and help in laying down collagen fibrils in the ground substance.

Over these collagen fibrils calcium and phosphates are deposited. The alkaline phos­phatase which is present in osteoblasts, breaks down organic phosphate esters to increase the calcium the phosphate level to a critical value. The precipitation occurring as a result of this changes to hydroxyapatite (Ca10 (PO4)6 (OH)2) and then gradually to dense bone.

Disc and Cartilage Biology

Traumatic and degenerative damage to the articular joint and intervertebral disc (IVD) are major causes of acute and chronic pain. However, the factors that contribute to the loss of function and the underlying pathophysiology are still poorly understood. In addition, present medical and surgical approaches do not address the underlying pathology and are often unsatisfactory. We investigate potential mechanisms leading to cartilage and IVD damage and identify tissue and systemic biomarkers of degeneration, which may serve as diagnostic and therapeutic targets we then evaluate novel biological treatments for repair and regeneration.

We have established a whole IVD organ culture system with the ability to maintain entire discs alive for several weeks under controlled nutrient and mechanical loading conditions. Within this IVD-specific bioreactor, we are investigating the beneficial or detrimental effects of nutrition, mechanical load, and/or biochemical factors on disc cell viability and metabolic activity.

Our ex-vivo IVD defect and degeneration models allow us to design and evaluate appropriate biological treatment strategies, including implantation/ homing of stem cells, delivery of anabolic, anti-catabolic or anti-inflammatory molecules, new biomaterials or combinations thereof. Data from ex vivo models are correlated to in vivo observations and clinical data to identify molecular markers of dysfunction. The goal is to develop functional therapies which, depending on the type of damage, will maintain or restore the mechanical properties of the disc, while cellular components will enhance the endogenous regenerative process.

To study the potential of new therapies for articular cartilage repair and regeneration, we have developed cartilage-specific bioreactor system applying multiaxial load to tissue-engineered constructs or osteochondral explants. The bioreactor mimics the load and motion characteristics of an articulating joint. Chondral and osteochondral defect and disease models enable us to test tailored treatments under physiologically relevant, mechanically loaded ex-vivo conditions. Cell- and material-based therapies as well as chondrogenic and anti-inflammatory factors are under investigation for cartilage repair and preservation.

Four station bioreactor system for controlled mechanical loading of intervertebral discs. One station of the bioreactor with sample holder for culturing and loading of whole intervertebral discs. Histological section of bovine intervertebral disc with fibrin based implant (af: annulus fibrosus np: nucleus pulposus f: fibrin). Cartilage bioreactor system for controlled mechanical stimulation of tissue engineered constructs or (osteo)chondral explants histological section of osteochondral explant with polyurethane-based implant.

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Structure and Composition of Articular Cartilage

Articular cartilage is hyaline cartilage and is 2 to 4 mm thick. Unlike most tissues, articular cartilage does not have blood vessels, nerves, or lymphatics. It is composed of a dense extracellular matrix (ECM) with a sparse distribution of highly specialized cells called chondrocytes. The ECM is principally composed of water, collagen, and proteoglycans, with other noncollagenous proteins and glycoproteins present in lesser amounts. 8,9 Together, these components help to retain water within the ECM, which is critical to maintain its unique mechanical properties.

Along with collagen fiber ultrastructure and ECM, chondrocytes contribute to the various zones of articular cartilage—the superficial zone, the middle zone, the deep zone, and the calcified zone ( Figure 2 ). Within each zone, 3 regions can be identified—the pericellular region, the territorial region, and the interterritorial region.

Schematic, cross-sectional diagram of healthy articular cartilage: A, cellular organization in the zones of articular cartilage B, collagen fiber architecture. (Copyright American Academy of Orthopaedic Surgeons. Reprinted from the Journal of the American Academy of Orthopaedic Surgeons, 19942:192-201 with permission. 11 )


The thin superficial (tangential) zone protects deeper layers from shear stresses and makes up approximately 10% to 20% of articular cartilage thickness. The collagen fibers of this zone (primarily, type II and IX collagen) are packed tightly and aligned parallel to the articular surface ( Figure 2 ). The superficial layer contains a relatively high number of flattened chondrocytes, and the integrity of this layer is imperative in the protection and maintenance of deeper layers. This zone is in contact with synovial fluid and is responsible for most of the tensile properties of cartilage, which enable it to resist the sheer, tensile, and compressive forces imposed by articulation.

Immediately deep to the superficial zone is the middle (transitional) zone, which provides an anatomic and functional bridge between the superficial and deep zones. The middle zone represents 40% to 60% of the total cartilage volume, and it contains proteoglycans and thicker collagen fibrils. In this layer, the collagen is organized obliquely, and the chondrocytes are spherical and at low density. Functionally, the middle zone is the first line of resistance to compressive forces.

The deep zone is responsible for providing the greatest resistance to compressive forces, given that collagen fibrils are arranged perpendicular to the articular surface. The deep zone contains the largest diameter collagen fibrils in a radial disposition, the highest proteoglycan content, and the lowest water concentration. The chondrocytes are typically arranged in columnar orientation, parallel to the collagen fibers and perpendicular to the joint line. The deep zone represents approximately 30% of articular cartilage volume.

The tide mark distinguishes the deep zone from the calcified cartilage. The deep zone is responsible for providing the greatest amount of resistance to compressive forces, given the high proteoglycan content. Of note, the collagen fibrils are arranged perpendicular to the articular cartilage. The calcified layer plays an integral role in securing the cartilage to bone, by anchoring the collagen fibrils of the deep zone to subchondral bone. In this zone, the cell population is scarce and chondrocytes are hypertrophic.


In addition to zonal variations in structure and composition, the matrix consists of several distinct regions based on proximity to the chondrocytes, composition, and collagen fibril diameter and organization. The ECM can be divided into pericellular, territorial, and interterritorial regions.

The pericellular matrix is a thin layer adjacent to the cell membrane, and it completely surrounds the chondrocyte. It contains mainly proteoglycans, as well as glycoproteins and other noncollagenous proteins. This matrix region may play a functional role to initiate signal transduction within cartilage with load bearing. 15

The territorial matrix surrounds the pericellular matrix it is composed mostly of fine collagen fibrils, forming a basketlike network around the cells. 21,48,54 This region is thicker than the pericellular matrix, and it has been proposed that the territorial matrix may protect the cartilage cells against mechanical stresses and may contribute to the resiliency of the articular cartilage structure and its ability to withstand substantial loads. 62

The interterritorial region is the largest of the 3 matrix regions it contributes most to the biomechanical properties of articular cartilage. 42 This region is characterized by the randomly oriented bundles of large collagen fibrils, arranged parallel to the surface of the superficial zone, obliquely in the middle zone, and perpendicular to the joint surface in the deep zone. Proteoglycans are abundant in the interterritorial zone.


The chondrocyte is the resident cell type in articular cartilage. Chondrocytes are highly specialized, metabolically active cells that play a unique role in the development, maintenance, and repair of the ECM. Chondrocytes originate from mesenchymal stem cells and constitute about 2% of the total volume of articular cartilage. 2 Chondrocytes vary in shape, number, and size, depending on the anatomical regions of the articular cartilage. The chondrocytes in the superficial zone are flatter and smaller and generally have a greater density than that of the cells deeper in the matrix ( Figure 2 ).

Each chondrocyte establishes a specialized microenvironment and is responsible for the turnover of the ECM in its immediate vicinity. This microenvironment essentially traps the chondrocyte within its own matrix and so prevents any migration to adjacent areas of cartilage. Rarely do chondrocytes form cell-to-cell contacts for direct signal transduction and communication between cells. They do, however, respond to a variety of stimuli, including growth factors, mechanical loads, piezoelectric forces, and hydrostatic pressures. 8 Unfortunately, chondrocytes have limited potential for replication, a factor that contributes to the limited intrinsic healing capacity of cartilage in response to injury. Chondrocyte survival depends on an optimal chemical and mechanical environment.

Extracellular Matrix

In normal articular cartilage, tissue fluid represents between 65% and 80% of the total weight. 46 Collagens and proteoglycans account for the remaining dry weight. Several other classes of molecules can be found in smaller amounts in the ECM these include lipids, phospholipids, noncollagenous proteins, and glycoproteins.


Water is the most abundant component of articular cartilage, contributing up to 80% of its wet weight. Approximately 30% of this water is associated with the intrafibrillar space within the collagen, although a small percentage is contained in the intracellular space. The remainder is contained in the pore space of the matrix. 35,63 Inorganic ions such as sodium, calcium, chloride, and potassium are dissolved in the tissue water. 29,30,33 The relative water concentration decreases from about 80% at the superficial zone to 65% in the deep zone. 9 The flow of water through the cartilage and across the articular surface helps to transport and distribute nutrients to chondrocytes, in addition to providing lubrication.

Much of the interfibrillar water appears to exist as a gel, and most of it may be moved through the ECM by applying a pressure gradient across the tissue or by compressing the solid matrix. 44,46 Frictional resistance against this flow through the matrix is very high thus, the permeability of the tissue is very low.

It is the combination of the frictional resistance to water flow and the pressurization of water within the matrix that forms the 2 basic mechanisms by which articular cartilage derives its ability to withstand significant loads, often multiple times one’s body weight.


Collagen is the most abundant structural macromolecule in ECM, and it makes up about 60% of the dry weight of cartilage. Type II collagen represents 90% to 95% of the collagen in ECM and forms fibrils and fibers intertwined with proteoglycan aggregates. Collagen types I, IV, V, VI, IX, and XI are also present but contribute only a minor proportion. The minor collagens help to form and stabilize the type II collagen fibril network.

There are at least 15 distinct collagen types composed of no fewer than 29 polypeptide chains. All members of the collagen family contain a region consisting of 3 polypeptide chains (α-chains) wound into a triple helix. The amino acid composition of polypeptide chains is primarily glycine and proline, with hydroxyproline providing stability via hydrogen bonds along the length of the molecule. The triple helix structure of the polypeptide chains provides articular cartilage with important shear and tensile properties, which help to stabilize the matrix. 33


Proteoglycans are heavily glycosolated protein monomers. In articular cartilage, they represent the second-largest group of macromolecules in the ECM and account for 10% to 15% of the wet weight. Proteoglycans consist of a protein core with 1 or more linear glycosaminoglycan chains covalently attached. These chains may be composed of more than 100 monosaccharides they extend out from the protein core, remaining separated from one another because of charge repulsion. Articular cartilage contains a variety of proteoglycans that are essential for normal function, including aggrecan, decorin, biglycan, and fibromodulin.

The largest in size and the most abundant by weight is aggrecan, a proteoglycan that possesses more than 100 chondroitin sulfate and keratin sulfate chains. Aggrecan is characterized by its ability to interact with hyaluronan (HA) to form large proteoglycan aggregates via link proteins 12 ( Figure 3 ). Aggrecan occupies the interfibrillar space of the cartilage ECM and provides cartilage with its osmotic properties, which are critical to its ability to resist compressive loads.

Extracellular matrix of articular cartilage. Two major load-bearing macromolecules are present in articular cartilage: collagens (mainly, type II) and proteoglycans (notably, aggrecan). Smaller classes of molecules, such as noncollagenous proteins and smaller proteoglycans, are present in smaller amounts. The interaction between the highly negatively charged cartilage proteoglycans and type II collagen provides the compressive and tensile strength of the tissue. (Reprinted with permission from Chen et al, 2006. 13 )

The nonaggregating proteoglycans are characterized by their ability to interact with collagen. Although decorin, biglycan, and fibromodulin are much smaller than aggrecan, they may be present in similar molar quantities. These molecules are closely related in protein structure however, they differ in glycosaminoglycan composition and function. Decorin and biglycan possess 1 and 2 dermatan sulfate chains, respectively, whereas fibromodulin possesses several keratin sulfate chains. Decorin and fibromodulin interact with the type II collagen fibrils in the matrix and play a role in fibrillogenesis and interfibril interactions. Biglycan is mainly found in the immediate surrounding of the chondrocytes, where they may interact with collagen VI.

Noncollagenous Proteins and Glycoproteins

Although a number of noncollagenous proteins and glycoproteins are found within articular cartilage, their specific function has not been fully characterized. Some of these molecules (such as fibronectin and CII, a chondrocyte surface protein) likely play a role in the organization and maintenance of the macromolecular structure of the ECM.


Cartilage is a form of connective tissue in which the ground substance is abundant and of a firmly gelated consistency that endows this tissue with unusual rigidity and resistance to compression. The cells of cartilage, called chondrocytes, are isolated in small lacunae within the matrix. Although cartilage is avascular, gaseous metabolites and nutrients can diffuse through the aqueous phase of the gel-like matrix to reach the cells. Cartilage is enclosed by the perichondrium, a dense fibrous layer lined by cells that have the capacity to secrete hyaline matrix. Cartilage grows by formation of additional matrix and incorporation of new cells from the inner chondrogenic layer of the perichondrium. In addition, the young chondrocytes retain the capacity to divide even after they become isolated in lacunae within the matrix. The daughter cells of these divisions secrete new matrix between them and move apart in separate lacunae. The capacity of cartilage for both appositional and interstitial growth makes it a favourable material for the skeleton of the rapidly growing embryo. The cartilaginous skeletal elements present in fetal life are subsequently replaced by bone.

Hyaline cartilage, the most widely distributed form, has a pearl-gray semitranslucent matrix containing randomly oriented collagen fibrils but relatively little elastin. It is normally found on surfaces of joints and in the cartilage making up the fetal skeleton. In elastic cartilage, on the other hand, the matrix has a pale yellow appearance owing to the abundance of elastic fibres embedded in its substance. This variant of cartilage is more flexible than hyaline cartilage and is found principally in the external ear and in the larynx and epiglottis. The third type, called fibrocartilage, has a large proportion of dense collagen bundles oriented parallel. Its cells occupy lacunae that are often arranged in rows between the coarse bundles of collagen. It is found in intervertebral disks, at sites of attachment of tendons to bone, and in the articular disks of certain joints. Any cartilage type may have foci of calcification.

Like other connective tissues, bone consists of cells, fibres, and ground substance, but, in addition, the extracellular components are impregnated with minute crystals of calcium phosphate in the form of the mineral hydroxyapatite. The mineralization of the matrix is responsible for the hardness of bone. It also provides a large reserve of calcium that can be drawn upon to meet unusual needs for this element elsewhere in the body. The structural organization of bone is adapted to give maximal strength for its weight-bearing function with minimum weight. There are bones strong enough to support the weight of an elephant and others light enough to give internal support and leverage to the wings of birds.

Classification of Connective Tissues

The three broad categories of connective tissue are classified according to the characteristics of their ground substance and the types of fibers found within the matrix (Table 1). Connective tissue proper includes loose connective tissue and dense connective tissue. Both tissues have a variety of cell types and protein fibers suspended in a viscous ground substance. Dense connective tissue is reinforced by bundles of fibers that provide tensile strength, elasticity, and protection. In loose connective tissue, the fibers are loosely organized, leaving large spaces in between. Supportive connective tissue&mdashbone and cartilage&mdashprovide structure and strength to the body and protect soft tissues. A few distinct cell types and densely packed fibers in a matrix characterize these tissues. In bone, the matrix is rigid and described as calcified because of the deposited calcium salts. In fluid connective tissue, in other words, lymph and blood, various specialized cells circulate in a watery fluid containing salts, nutrients, and dissolved proteins.

  • Areolar
  • Adipose
  • Reticular
  • Hyaline
  • Fibrocartilage
  • Elastic
  • Regular elastic
  • Irregular elastic
  • Compact bone
  • Cancellous bone

BIO 140 - Human Biology I - Textbook

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Chapter 13

Connective Tissue Supports and Protects

  • Identify and distinguish between the types of connective tissue: proper, supportive, and fluid
  • Explain the functions of connective tissues

As may be obvious from its name, one of the major functions of connective tissue is to connect tissues and organs. Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix . The matrix usually includes a large amount of extracellular material produced by the connective tissue cells that are embedded within it. The matrix plays a major role in the functioning of this tissue. The major component of the matrix is a ground substance often crisscrossed by protein fibers. This ground substance is usually a fluid, but it can also be mineralized and solid, as in bones. Connective tissues come in a vast variety of forms, yet they typically have in common three characteristic components: cells, large amounts of amorphous ground substance, and protein fibers. The amount and structure of each component correlates with the function of the tissue, from the rigid ground substance in bones supporting the body to the inclusion of specialized cells for example, a phagocytic cell that engulfs pathogens and also rids tissue of cellular debris.

Functions of Connective Tissues

Connective tissues perform many functions in the body, but most importantly, they support and connect other tissues from the connective tissue sheath that surrounds muscle cells, to the tendons that attach muscles to bones, and to the skeleton that supports the positions of the body. Protection is another major function of connective tissue, in the form of fibrous capsules and bones that protect delicate organs and, of course, the skeletal system. Specialized cells in connective tissue defend the body from microorganisms that enter the body. Transport of fluid, nutrients, waste, and chemical messengers is ensured by specialized fluid connective tissues, such as blood and lymph. Adipose cells store surplus energy in the form of fat and contribute to the thermal insulation of the body.

Embryonic Connective Tissue

All connective tissues derive from the mesodermal layer of the embryo (see [link] ). The first connective tissue to develop in the embryo is mesenchyme , the stem cell line from which all connective tissues are later derived. Clusters of mesenchymal cells are scattered throughout adult tissue and supply the cells needed for replacement and repair after a connective tissue injury. A second type of embryonic connective tissue forms in the umbilical cord, called mucous connective tissue or Wharton&rsquos jelly. This tissue is no longer present after birth, leaving only scattered mesenchymal cells throughout the body.

Classification of Connective Tissues

The three broad categories of connective tissue are classified according to the characteristics of their ground substance and the types of fibers found within the matrix (Table). Connective tissue proper includes loose connective tissue and dense connective tissue . Both tissues have a variety of cell types and protein fibers suspended in a viscous ground substance. Dense connective tissue is reinforced by bundles of fibers that provide tensile strength, elasticity, and protection. In loose connective tissue, the fibers are loosely organized, leaving large spaces in between. Supportive connective tissue &mdashbone and cartilage&mdashprovide structure and strength to the body and protect soft tissues. A few distinct cell types and densely packed fibers in a matrix characterize these tissues. In bone, the matrix is rigid and described as calcified because of the deposited calcium salts. In fluid connective tissue , in other words, lymph and blood, various specialized cells circulate in a watery fluid containing salts, nutrients, and dissolved proteins.

Table 1: Connective Tissue Examples

Connective Tissue Proper

Fibroblasts are present in all connective tissue proper (Figure 1). Fibrocytes, adipocytes, and mesenchymal cells are fixed cells, which means they remain within the connective tissue. Other cells move in and out of the connective tissue in response to chemical signals. Macrophages, mast cells, lymphocytes, plasma cells, and phagocytic cells are found in connective tissue proper but are actually part of the immune system protecting the body.

Figure 1: Fibroblasts produce this fibrous tissue. Connective tissue proper includes the fixed cells fibrocytes, adipocytes, and mesenchymal cells. LM × 400. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

Cell Types

The most abundant cell in connective tissue proper is the fibroblast . Polysaccharides and proteins secreted by fibroblasts combine with extra-cellular fluids to produce a viscous ground substance that, with embedded fibrous proteins, forms the extra-cellular matrix. As you might expect, a fibrocyte , a less active form of fibroblast, is the second most common cell type in connective tissue proper.

Adipocytes are cells that store lipids as droplets that fill most of the cytoplasm. There are two basic types of adipocytes: white and brown. The brown adipocytes store lipids as many droplets, and have high metabolic activity. In contrast, white fat adipocytes store lipids as a single large drop and are metabolically less active. Their effectiveness at storing large amounts of fat is witnessed in obese individuals. The number and type of adipocytes depends on the tissue and location, and vary among individuals in the population.

The mesenchymal cell is a multipotent adult stem cell. These cells can differentiate into any type of connective tissue cells needed for repair and healing of damaged tissue.

The macrophage cell is a large cell derived from a monocyte, a type of blood cell, which enters the connective tissue matrix from the blood vessels. The macrophage cells are an essential component of the immune system, which is the body&rsquos defense against potential pathogens and degraded host cells. When stimulated, macrophages release cytokines, small proteins that act as chemical messengers. Cytokines recruit other cells of the immune system to infected sites and stimulate their activities. Roaming, or free, macrophages move rapidly by amoeboid movement, engulfing infectious agents and cellular debris. In contrast, fixed macrophages are permanent residents of their tissues.

The mast cell, found in connective tissue proper, has many cytoplasmic granules. These granules contain the chemical signals histamine and heparin. When irritated or damaged, mast cells release histamine, an inflammatory mediator, which causes vasodilation and increased blood flow at a site of injury or infection, along with itching, swelling, and redness you recognize as an allergic response. Like blood cells, mast cells are derived from hematopoietic stem cells and are part of the immune system.

Connective Tissue Fibers and Ground Substance

Three main types of fibers are secreted by fibroblasts: collagen fibers, elastic fibers, and reticular fibers. Collagen fiber is made from fibrous protein subunits linked together to form a long and straight fiber. Collagen fibers, while flexible, have great tensile strength, resist stretching, and give ligaments and tendons their characteristic resilience and strength. These fibers hold connective tissues together, even during the movement of the body.

Elastic fiber contains the protein elastin along with lesser amounts of other proteins and glycoproteins. The main property of elastin is that after being stretched or compressed, it will return to its original shape. Elastic fibers are prominent in elastic tissues found in skin and the elastic ligaments of the vertebral column.

Reticular fiber is also formed from the same protein subunits as collagen fibers however, these fibers remain narrow and are arrayed in a branching network. They are found throughout the body, but are most abundant in the reticular tissue of soft organs, such as liver and spleen, where they anchor and provide structural support to the parenchyma (the functional cells, blood vessels, and nerves of the organ).

All of these fiber types are embedded in ground substance. Secreted by fibroblasts, ground substance is made of polysaccharides, specifically hyaluronic acid, and proteins. These combine to form a proteoglycan with a protein core and polysaccharide branches. The proteoglycan attracts and traps available moisture forming the clear, viscous, colorless matrix you now know as ground substance.

Loose Connective Tissue

Loose connective tissue is found between many organs where it acts both to absorb shock and bind tissues together. It allows water, salts, and various nutrients to diffuse through to adjacent or imbedded cells and tissues.

Adipose tissue consists mostly of fat storage cells, with little extracellular matrix (Figure 2 ). A large number of capillaries allow rapid storage and mobilization of lipid molecules. White adipose tissue is most abundant. It can appear yellow and owes its color to carotene and related pigments from plant food. White fat contributes mostly to lipid storage and can serve as insulation from cold temperatures and mechanical injuries. White adipose tissue can be found protecting the kidneys and cushioning the back of the eye. Brown adipose tissue is more common in infants, hence the term &ldquobaby fat.&rdquo In adults, there is a reduced amount of brown fat and it is found mainly in the neck and clavicular regions of the body. The many mitochondria in the cytoplasm of brown adipose tissue help explain its efficiency at metabolizing stored fat. Brown adipose tissue is thermogenic, meaning that as it breaks down fats, it releases metabolic heat, rather than producing adenosine triphosphate (ATP), a key molecule used in metabolism.

Figure 2: This is a loose connective tissue that consists of fat cells with little extracellular matrix. It stores fat for energy and provides insulation. LM × 800. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

Areolar tissue shows little specialization. It contains all the cell types and fibers previously described and is distributed in a random, web-like fashion. It fills the spaces between muscle fibers, surrounds blood and lymph vessels, and supports organs in the abdominal cavity. Areolar tissue underlies most epithelia and represents the connective tissue component of epithelial membranes, which are described further in a later section.

Reticular tissue is a mesh-like, supportive framework for soft organs such as lymphatic tissue, the spleen, and the liver (Figure 3). Reticular cells produce the reticular fibers that form the network onto which other cells attach. It derives its name from the Latin reticulus, which means &ldquolittle net.&rdquo

Figure 3: This is a loose connective tissue made up of a network of reticular fibers that provides a supportive framework for soft organs. LM × 1600. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

Dense Connective Tissue

Dense connective tissue contains more collagen fibers than does loose connective tissue. As a consequence, it displays greater resistance to stretching. There are two major categories of dense connective tissue: regular and irregular. Dense regular connective tissue fibers are parallel to each other, enhancing tensile strength and resistance to stretching in the direction of the fiber orientations. Ligaments and tendons are made of dense regular connective tissue, but in ligaments not all fibers are parallel. Dense regular elastic tissue contains elastin fibers in addition to collagen fibers, which allows the ligament to return to its original length after stretching. The ligaments in the vocal folds and between the vertebrae in the vertebral column are elastic.

In dense irregular connective tissue, the direction of fibers is random. This arrangement gives the tissue greater strength in all directions and less strength in one particular direction. In some tissues, fibers crisscross and form a mesh. In other tissues, stretching in several directions is achieved by alternating layers where fibers run in the same orientation in each layer, and it is the layers themselves that are stacked at an angle. The dermis of the skin is an example of dense irregular connective tissue rich in collagen fibers. Dense irregular elastic tissues give arterial walls the strength and the ability to regain original shape after stretching (Figure 4).

Dense Connective Tissue

Figure 4: (a) Dense regular connective tissue consists of collagenous fibers packed into parallel bundles. (b) Dense irregular connective tissue consists of collagenous fibers interwoven into a mesh-like network. From top, LM × 1000, LM × 200. (Micrographs provided by the Regents of University of Michigan Medical School © 2012)

Disorders of the&hellip

Connective Tissue: Tendinitis

Your opponent stands ready as you prepare to hit the serve, but you are confident that you will smash the ball past your opponent. As you toss the ball high in the air, a burning pain shoots across your wrist and you drop the tennis racket. That dull ache in the wrist that you ignored through the summer is now an unbearable pain. The game is over for now.

After examining your swollen wrist, the doctor in the emergency room announces that you have developed wrist tendinitis. She recommends icing the tender area, taking non-steroidal anti-inflammatory medication to ease the pain and to reduce swelling, and complete rest for a few weeks. She interrupts your protests that you cannot stop playing. She issues a stern warning about the risk of aggravating the condition and the possibility of surgery. She consoles you by mentioning that well known tennis players such as Venus and Serena Williams and Rafael Nadal have also suffered from tendinitis related injuries.

What is tendinitis and how did it happen? Tendinitis is the inflammation of a tendon, the thick band of fibrous connective tissue that attaches a muscle to a bone. The condition causes pain and tenderness in the area around a joint. On rare occasions, a sudden serious injury will cause tendinitis. Most often, the condition results from repetitive motions over time that strain the tendons needed to perform the tasks.

Persons whose jobs and hobbies involve performing the same movements over and over again are often at the greatest risk of tendinitis. You hear of tennis and golfer&rsquos elbow, jumper's knee, and swimmer&rsquos shoulder. In all cases, overuse of the joint causes a microtrauma that initiates the inflammatory response. Tendinitis is routinely diagnosed through a clinical examination. In case of severe pain, X-rays can be examined to rule out the possibility of a bone injury. Severe cases of tendinitis can even tear loose a tendon. Surgical repair of a tendon is painful. Connective tissue in the tendon does not have abundant blood supply and heals slowly.

While older adults are at risk for tendinitis because the elasticity of tendon tissue decreases with age, active people of all ages can develop tendinitis. Young athletes, dancers, and computer operators anyone who performs the same movements constantly is at risk for tendinitis. Although repetitive motions are unavoidable in many activities and may lead to tendinitis, precautions can be taken that can lessen the probability of developing tendinitis. For active individuals, stretches before exercising and cross training or changing exercises are recommended. For the passionate athlete, it may be time to take some lessons to improve technique. All of the preventive measures aim to increase the strength of the tendon and decrease the stress put on it. With proper rest and managed care, you will be back on the court to hit that slice-spin serve over the net.

Supportive Connective Tissues

Two major forms of supportive connective tissue, cartilage and bone, allow the body to maintain its posture and protect internal organs.


The distinctive appearance of cartilage is due to polysaccharides called chondroitin sulfates, which bind with ground substance proteins to form proteoglycans. Embedded within the cartilage matrix are chondrocytes , or cartilage cells, and the space they occupy are called lacunae (singular = lacuna). A layer of dense irregular connective tissue, the perichondrium, encapsulates the cartilage. Cartilaginous tissue is avascular, thus all nutrients need to diffuse through the matrix to reach the chondrocytes. This is a factor contributing to the very slow healing of cartilaginous tissues.

The three main types of cartilage tissue are hyaline cartilage, fibrocartilage, and elastic cartilage (Figure 5). Hyaline cartilage , the most common type of cartilage in the body, consists of short and dispersed collagen fibers and contains large amounts of proteoglycans. Under the microscope, tissue samples appear clear. The surface of hyaline cartilage is smooth. Both strong and flexible, it is found in the rib cage and nose and covers bones where they meet to form moveable joints. It makes up a template of the embryonic skeleton before bone formation. A plate of hyaline cartilage at the ends of bone allows continued growth until adulthood. Fibrocartilage is tough because it has thick bundles of collagen fibers dispersed through its matrix. Menisci in the knee joint and the intervertebral discs are examples of fibrocartilage. Elastic cartilage contains elastic fibers as well as collagen and proteoglycans. This tissue gives rigid support as well as elasticity. Tug gently at your ear lobes, and notice that the lobes return to their initial shape. The external ear contains elastic cartilage.

Figure 5: Cartilage is a connective tissue consisting of collagenous fibers embedded in a firm matrix of chondroitin sulfates. (a) Hyaline cartilage provides support with some flexibility. The example is from dog tissue. (b) Fibrocartilage provides some compressibility and can absorb pressure. (c) Elastic cartilage provides firm but elastic support. From top, LM × 300, LM × 1200, LM × 1016. (Micrographs provided by the Regents of University of Michigan Medical School © 2012)


Bone is the hardest connective tissue. It provides protection to internal organs and supports the body. Bone&rsquos rigid extracellular matrix contains mostly collagen fibers embedded in a mineralized ground substance containing hydroxyapatite, a form of calcium phosphate. Both components of the matrix, organic and inorganic, contribute to the unusual properties of bone. Without collagen, bones would be brittle and shatter easily. Without mineral crystals, bones would flex and provide little support. Osteocytes, bone cells like chondrocytes, are located within lacunae. The histology of transverse tissue from long bone shows a typical arrangement of osteocytes in concentric circles around a central canal. Bone is a highly vascularized tissue. Unlike cartilage, bone tissue can recover from injuries in a relatively short time.

Cancellous bone looks like a sponge under the microscope and contains empty spaces between trabeculae, or arches of bone proper. It is lighter than compact bone and found in the interior of some bones and at the end of long bones. Compact bone is solid and has greater structural strength.

Fluid Connective Tissue

Blood and lymph are fluid connective tissues. Cells circulate in a liquid extracellular matrix. The formed elements circulating in blood are all derived from hematopoietic stem cells located in bone marrow (Figure 6). Erythrocytes, red blood cells, transport oxygen and some carbon dioxide. Leukocytes, white blood cells, are responsible for defending against potentially harmful microorganisms or molecules. Platelets are cell fragments involved in blood clotting. Some white blood cells have the ability to cross the endothelial layer that lines blood vessels and enter adjacent tissues. Nutrients, salts, and wastes are dissolved in the liquid matrix and transported through the body.

Lymph contains a liquid matrix and white blood cells. Lymphatic capillaries are extremely permeable, allowing larger molecules and excess fluid from interstitial spaces to enter the lymphatic vessels. Lymph drains into blood vessels, delivering molecules to the blood that could not otherwise directly enter the bloodstream. In this way, specialized lymphatic capillaries transport absorbed fats away from the intestine and deliver these molecules to the blood.

Figure 6: Blood is a fluid connective tissue containing erythrocytes and various types of leukocytes that circulate in a liquid extracellular matrix. LM × 1600. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

Chapter Review

Connective tissue is a heterogeneous tissue with many cell shapes and tissue architecture. Structurally, all connective tissues contain cells that are embedded in an extracellular matrix stabilized by proteins. The chemical nature and physical layout of the extracellular matrix and proteins vary enormously among tissues, reflecting the variety of functions that connective tissue fulfills in the body. Connective tissues separate and cushion organs, protecting them from shifting or traumatic injury. Connect tissues provide support and assist movement, store and transport energy molecules, protect against infections, and contribute to temperature homeostasis.

Many different cells contribute to the formation of connective tissues. They originate in the mesodermal germ layer and differentiate from mesenchyme and hematopoietic tissue in the bone marrow. Fibroblasts are the most abundant and secrete many protein fibers, adipocytes specialize in fat storage, hematopoietic cells from the bone marrow give rise to all the blood cells, chondrocytes form cartilage, and osteocytes form bone. The extracellular matrix contains fluid, proteins, polysaccharide derivatives, and, in the case of bone, mineral crystals. Protein fibers fall into three major groups: collagen fibers that are thick, strong, flexible, and resist stretch reticular fibers that are thin and form a supportive mesh and elastin fibers that are thin and elastic.

The major types of connective tissue are connective tissue proper, supportive tissue, and fluid tissue. Loose connective tissue proper includes adipose tissue, areolar tissue, and reticular tissue. These serve to hold organs and other tissues in place and, in the case of adipose tissue, isolate and store energy reserves. The matrix is the most abundant feature for loose tissue although adipose tissue does not have much extracellular matrix. Dense connective tissue proper is richer in fibers and may be regular, with fibers oriented in parallel as in ligaments and tendons, or irregular, with fibers oriented in several directions. Organ capsules (collagenous type) and walls of arteries (elastic type) contain dense irregular connective tissue. Cartilage and bone are supportive tissue. Cartilage contains chondrocytes and is somewhat flexible. Hyaline cartilage is smooth and clear, covers joints, and is found in the growing portion of bones. Fibrocartilage is tough because of extra collagen fibers and forms, among other things, the intervertebral discs. Elastic cartilage can stretch and recoil to its original shape because of its high content of elastic fibers. The matrix contains very few blood vessels. Bones are made of a rigid, mineralized matrix containing calcium salts, crystals, and osteocytes lodged in lacunae. Bone tissue is highly vascularized. Cancellous bone is spongy and less solid than compact bone. Fluid tissue, for example blood and lymph, is characterized by a liquid matrix and no supporting fibers.

Watch the video: Cartilage Science Explained (August 2022).