Cartilage

Last updated
Cartilage
Hypertrophic Zone of Epiphyseal Plate.jpg
Light micrograph of undecalcified hyaline cartilage showing chondrocytes and organelles, lacunae and matrix.
Identifiers
MeSH D002356
TA98 A02.0.00.005
TA2 381
Anatomical terminology

Cartilage is a resilient and smooth type of connective tissue. Semi-transparent and non-porous, it is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, [1] and is a structural component of many body parts including the rib cage, the neck and the bronchial tubes, and the intervertebral discs. In other taxa, such as chondrichthyans and cyclostomes, it constitutes a much greater proportion of the skeleton. [2] It is not as hard and rigid as bone, but it is much stiffer and much less flexible than muscle. The matrix of cartilage is made up of glycosaminoglycans, proteoglycans, collagen fibers and, sometimes, elastin. It usually grows quicker than bone.

Contents

Because of its rigidity, cartilage often serves the purpose of holding tubes open in the body. Examples include the rings of the trachea, such as the cricoid cartilage and carina.

Cartilage is composed of specialized cells called chondrocytes that produce a large amount of collagenous extracellular matrix, abundant ground substance that is rich in proteoglycan and elastin fibers. Cartilage is classified into three types — elastic cartilage, hyaline cartilage, and fibrocartilage — which differ in their relative amounts of collagen and proteoglycan.

As cartilage does not contain blood vessels or nerves, it is insensitive. However, some fibrocartilage such as the meniscus of the knee has partial blood supply. Nutrition is supplied to the chondrocytes by diffusion. The compression of the articular cartilage or flexion of the elastic cartilage generates fluid flow, which assists the diffusion of nutrients to the chondrocytes. Compared to other connective tissues, cartilage has a very slow turnover of its extracellular matrix and is documented to repair at only a very slow rate relative to other tissues.

There are three different types of cartilage: elastic (A), hyaline (B), and fibrous (C). In elastic cartilage, the cells are closer together creating less intercellular space. Elastic cartilage is found in the external ear flaps and in parts of the larynx. Hyaline cartilage has fewer cells than elastic cartilage; there is more intercellular space. Hyaline cartilage is found in the nose, ears, trachea, parts of the larynx, and smaller respiratory tubes. Fibrous cartilage has the fewest cells so it has the most intercellular space. Fibrous cartilage is found in the spine and the menisci. Cartilage types.jpg
There are three different types of cartilage: elastic (A), hyaline (B), and fibrous (C). In elastic cartilage, the cells are closer together creating less intercellular space. Elastic cartilage is found in the external ear flaps and in parts of the larynx. Hyaline cartilage has fewer cells than elastic cartilage; there is more intercellular space. Hyaline cartilage is found in the nose, ears, trachea, parts of the larynx, and smaller respiratory tubes. Fibrous cartilage has the fewest cells so it has the most intercellular space. Fibrous cartilage is found in the spine and the menisci.

Structure

Development

In embryogenesis, the skeletal system is derived from the mesoderm germ layer. Chondrification (also known as chondrogenesis) is the process by which cartilage is formed from condensed mesenchyme tissue, which differentiates into chondroblasts and begins secreting the molecules (aggrecan and collagen type II) that form the extracellular matrix. In all vertebrates, cartilage is the main skeletal tissue in early ontogenetic stages; [3] [4] in osteichthyans, many cartilaginous elements subsequently ossify through endochondral and perichondral ossification. [5]

Following the initial chondrification that occurs during embryogenesis, cartilage growth consists mostly of the maturing of immature cartilage to a more mature state. The division of cells within cartilage occurs very slowly, and thus growth in cartilage is usually not based on an increase in size or mass of the cartilage itself. [6] It has been identified that non-coding RNAs (e.g. miRNAs and long non-coding RNAs) as the most important epigenetic modulators can affect the chondrogenesis. This also justifies the non-coding RNAs' contribution in various cartilage-dependent pathological conditions such as arthritis, and so on. [7]

Articular cartilage

Section from mouse joint showing cartilage (purple) Cartilage from mouse joint.jpg
Section from mouse joint showing cartilage (purple)

The articular cartilage function is dependent on the molecular composition of the extracellular matrix (ECM). The ECM consists mainly of proteoglycan and collagens. The main proteoglycan in cartilage is aggrecan, which, as its name suggests, forms large aggregates with hyaluronan and with itself. [8] These aggregates are negatively charged and hold water in the tissue. The collagen, mostly collagen type II, constrains the proteoglycans. The ECM responds to tensile and compressive forces that are experienced by the cartilage. [9] Cartilage growth thus refers to the matrix deposition, but can also refer to both the growth and remodeling of the extracellular matrix. Due to the great stress on the patellofemoral joint during resisted knee extension, the articular cartilage of the patella is among the thickest in the human body. The ECM of articular cartilage is classified into three regions: the pericellular matrix, the territorial matrix, and the interterritorial matrix.

Function

Mechanical properties

The mechanical properties of articular cartilage in load-bearing joints such as the knee and hip have been studied extensively at macro, micro, and nano-scales. These mechanical properties include the response of cartilage in frictional, compressive, shear and tensile loading. Cartilage is resilient and displays viscoelastic properties. [10]

Since cartilage has interstitial fluid that is free-moving, it makes the material difficult to test. One of the tests commonly used to overcome this obstacle is a confined compression test, which can be used in either a 'creep' or 'relaxation' mode. [11] [12] In creep mode, the tissue displacement is measured as a function of time under a constant load, and in relaxation mode, the force is measured as a function of time under constant displacement. In creep mode, the tissue displacement is measured as a function of time under a constant load. During this mode, the deformation of the tissue has two main regions. In the first region, the displacement is rapid due to the initial flow of fluid out of the cartilage, and in the second region, the displacement slows down to an eventual constant equilibrium value. Under the commonly used loading conditions, the equilibrium displacement can take hours to reach.

In both the creep mode and the relaxation mode of a confined compression test, a disc of cartilage is placed in an impervious, fluid-filled container and covered with a porous plate that restricts the flow of interstitial fluid to the vertical direction. This test can be used to measure the aggregate modulus of cartilage, which is typically in the range of 0.5 to 0.9 MPa for articular cartilage, [11] [12] [13] and the Young’s Modulus, which is typically 0.45 to 0.80 MPa. [11] [13] The aggregate modulus is “a measure of the stiffness of the tissue at equilibrium when all fluid flow has ceased”, [11] and Young’s modulus is a measure of how much a material strains (changes length) under a given stress.

The confined compression test can also be used to measure permeability, which is defined as the resistance to fluid flow through a material. Higher permeability allows for fluid to flow out of a material’s matrix more rapidly, while lower permeability leads to an initial rapid fluid flow and a slow decrease to equilibrium. Typically, the permeability of articular cartilage is in the range of 10^-15 to 10^-16 m^4/Ns. [11] [12] However, permeability is sensitive to loading conditions and testing location. For example, permeability varies throughout articular cartilage and tends to be highest near the joint surface and lowest near the bone (or “deep zone”). Permeability also decreases under increased loading of the tissue.

Indentation testing is an additional type of test commonly used to characterize cartilage. [11] [14] Indentation testing involves using an indentor (usually <0.8 mm) to measure the displacement of the tissue under constant load. Similar to confined compression testing, it may take hours to reach equilibrium displacement. This method of testing can be used to measure the aggregate modulus, Poisson's ratio, and permeability of the tissue. Initially, there was a misconception that due to its predominantly water-based composition, cartilage had a Poisson's ratio of 0.5 and should be modeled as an incompressible material. [11] However, subsequent research has disproven this belief. The Poisson’s ratio of articular cartilage has been measured to be around 0.4 or lower in humans [11] [14] and ranges from 0.46–0.5 in bovine subjects. [15]

The mechanical properties of articular cartilage are largely anisotropic, test-dependent, and can be age-dependent. [11] These properties also depend on collagen-proteoglycan interactions and therefore can increase/decrease depending on the total content of water, collagen, glycoproteins, etc. For example, increased glucosaminoglycan content leads to an increase in compressive stiffness, and increased water content leads to a lower aggregate modulus.

Tendon-bone interface

In addition to its role in load-bearing joints, cartilage serves a crucial function as a gradient material between softer tissues and bone. Mechanical gradients are crucial for your body’s function, and for complex artificial structures including joint implants. Interfaces with mismatched material properties lead to areas of high stress concentration which, over the millions of loading cycles experienced by human joins over a lifetime, would eventually lead to failure. For example, the elastic modulus of human bone is roughly 20 GPa while the softer regions of cartilage can be about 0.5 to 0.9 MPa. [16] [17] When there is a smooth gradient of materials properties, however, stresses are distributed evenly across the interface, which puts less wear on each individual part.

The body solves this problem with stiffer, higher modulus layers near bone, with high concentrations of mineral deposits such as hydroxyapatite. Collagen fibers (which provide mechanical stiffness in cartilage) in this region are anchored directly to bones, reducing the possible deformation. Moving closer to soft tissue into the region known as the tidemark, the density of chondrocytes increases and collagen fibers are rearranged to optimize for stress dissipation and low friction. The outermost layer near the articular surface is known as the superficial zone, which primarily serves as a lubrication region. Here cartilage is characterized by a dense extracellular matrix and is rich in proteoglycans (which dispel and reabsorb water to soften impacts) and thin collagen oriented parallel to the joint surface which have excellent shear resistant properties. [18]

Osteoarthritis and natural aging both have negative effects on cartilage as a whole as well as the proper function of the materials gradient within. The earliest changes are often in the superficial zone, the softest and most lubricating part of the tissue. Degradation of this layer can put additional stresses on deeper layers which are not designed to support the same deformations. Another common effect of aging is increased crosslinking of collagen fibers. This leads to stiffer cartilage as a whole, which again can lead to early failure as stiffer tissue is more susceptible to fatigue based failure. Aging in calcified regions also generally leads to a larger number of mineral deposits, which has a similarly undesired stiffening effect. [19] Osteoarthritis has more extreme effects and can entirely wear down cartilage, causing direct bone-to-bone contact. [20]

Frictional properties

Lubricin, a glycoprotein abundant in cartilage and synovial fluid, plays a major role in bio-lubrication and wear protection of cartilage. [21]

Repair

Cartilage has limited repair capabilities: Because chondrocytes are bound in lacunae, they cannot migrate to damaged areas. Therefore, cartilage damage is difficult to heal. Also, because hyaline cartilage does not have a blood supply, the deposition of new matrix is slow. Over the last years, surgeons and scientists have elaborated a series of cartilage repair procedures that help to postpone the need for joint replacement. A tear of the meniscus of the knee cartilage can often be surgically trimmed to reduce problems. Complete healing of cartilage after injury or repair procedures is hindered by cartilage-specific inflammation caused by the involvement of M1/M2 macrophages, mast cells, and their intercellular interactions. [22]

Biological engineering techniques are being developed to generate new cartilage, using a cellular "scaffolding" material and cultured cells to grow artificial cartilage. [23] Extensive researches have been conducted on freeze-thawed PVA hydrogels as a base material for such a purpose. [24] These gels have exhibited great promises in terms of biocompatibility, wear resistance, shock absorption, friction coefficient, flexibility, and lubrication, and thus are considered superior to polyethylene-based cartilages. A two-year implantation of the PVA hydrogels as artificial meniscus in rabbits showed that the gels remain intact without degradation, fracture, or loss of properties. [24]

Clinical significance

Human skeleton with articular cartilage shown in blue Skeleton 1 -- Smart-Servier.png
Human skeleton with articular cartilage shown in blue

Disease

Several diseases can affect cartilage. Chondrodystrophies are a group of diseases, characterized by the disturbance of growth and subsequent ossification of cartilage. Some common diseases that affect the cartilage are listed below.

Tumors made up of cartilage tissue, either benign or malignant, can occur. They usually appear in bone, rarely in pre-existing cartilage. The benign tumors are called chondroma, the malignant ones chondrosarcoma. Tumors arising from other tissues may also produce a cartilage-like matrix, the best-known being pleomorphic adenoma of the salivary glands.

The matrix of cartilage acts as a barrier, preventing the entry of lymphocytes or diffusion of immunoglobulins. This property allows for the transplantation of cartilage from one individual to another without fear of tissue rejection.

Imaging

Cartilage does not absorb X-rays under normal in vivo conditions, but a dye can be injected into the synovial membrane that will cause the X-rays to be absorbed by the dye. The resulting void on the radiographic film between the bone and meniscus represents the cartilage. For in vitro X-ray scans, the outer soft tissue is most likely removed, so the cartilage and air boundary are enough to contrast the presence of cartilage due to the refraction of the X-ray. [27]

Histological image of hyaline cartilage stained with haematoxylin and eosin, under polarized light Cartilage polarised.jpg
Histological image of hyaline cartilage stained with haematoxylin and eosin, under polarized light

Other animals

Cartilaginous fish

Cartilaginous fish (Chondrichthyes) or sharks, rays and chimaeras have a skeleton composed entirely of cartilage.

Invertebrate cartilage

Cartilage tissue can also be found among some arthropods such as horseshoe crabs, some mollusks such as marine snails and cephalopods, and some annelids like sabellid polychaetes.

Arthropods

The most studied cartilage in arthropods is the branchial cartilage of Limulus polyphemus . It is a vesicular cell-rich cartilage due to the large, spherical and vacuolated chondrocytes with no homologies in other arthropods. Other type of cartilage found in L. polyphemus is the endosternite cartilage, a fibrous-hyaline cartilage with chondrocytes of typical morphology in a fibrous component, much more fibrous than vertebrate hyaline cartilage, with mucopolysaccharides immunoreactive against chondroitin sulfate antibodies. There are homologous tissues to the endosternite cartilage in other arthropods. [28] The embryos of Limulus polyphemus express ColA and hyaluronan in the gill cartilage and the endosternite, which indicates that these tissues are fibrillar-collagen-based cartilage. The endosternite cartilage forms close to Hh-expressing ventral nerve cords and expresses ColA and SoxE, a Sox9 analog. This is also seen in gill cartilage tissue. [29]

Mollusks

In cephalopods, the models used for the studies of cartilage are Octopus vulgaris and Sepia officinalis . The cephalopod cranial cartilage is the invertebrate cartilage that shows more resemblance to the vertebrate hyaline cartilage. The growth is thought to take place throughout the movement of cells from the periphery to the center. The chondrocytes present different morphologies related to their position in the tissue. [28] The embryos of S. officinalis express ColAa, ColAb, and hyaluronan in the cranial cartilages and other regions of chondrogenesis. This implies that the cartilage is fibrillar-collagen-based. The S. officinalis embryo expresses hh, whose presence causes ColAa and ColAb expression and is also able to maintain proliferating cells undiferentiated. It has been observed that this species presents the expression SoxD and SoxE, analogs of the vertebrate Sox5/6 and Sox9, in the developing cartilage. The cartilage growth pattern is the same as in vertebrate cartilage. [29]

In gastropods, the interest lies in the odontophore, a cartilaginous structure that supports the radula. The most studied species regarding this particular tissue is Busycotypus canaliculatus . The odontophore is a vesicular cell rich cartilage, consisting of vacuolated cells containing myoglobin, surrounded by a low amount of extra cellular matrix containing collagen. The odontophore contains muscle cells along with the chondrocytes in the case of Lymnaea and other mollusks that graze vegetation. [28]

Sabellid polychaetes

The sabellid polychaetes, or feather duster worms, have cartilage tissue with cellular and matrix specialization supporting their tentacles. They present two distinct extracellular matrix regions. These regions are an acellular fibrous region with a high collagen content, called cartilage-like matrix, and collagen lacking a highly cellularized core, called osteoid-like matrix. The cartilage-like matrix surrounds the osteoid-like matrix. The amount of the acellular fibrous region is variable. The model organisms used in the study of cartilage in sabellid polychaetes are Potamilla species and Myxicola infundibulum . [28]

Plants and fungi

Vascular plants, particularly seeds, and the stems of some mushrooms, are sometimes called "cartilaginous", although they contain no cartilage. [30]

Related Research Articles

<span class="mw-page-title-main">Extracellular matrix</span> Network of proteins and molecules outside cells that provides structural support for cells

In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and biochemical support to surrounding cells. Because multicellularity evolved independently in different multicellular lineages, the composition of ECM varies between multicellular structures; however, cell adhesion, cell-to-cell communication and differentiation are common functions of the ECM.

<span class="mw-page-title-main">Hyaline cartilage</span> Type of cartilage in animals

Hyaline cartilage is the glass-like (hyaline) and translucent cartilage found on many joint surfaces. It is also most commonly found in the ribs, nose, larynx, and trachea. Hyaline cartilage is pearl-gray in color, with a firm consistency and has a considerable amount of collagen. It contains no nerves or blood vessels, and its structure is relatively simple.

<span class="mw-page-title-main">Elastic cartilage</span>

Elastic cartilage, fibroelastic cartilage or yellow fibrocartilage is a type of cartilage present in the pinnae (auricles) of the ear giving it shape, provides shape for the lateral region of the external auditory meatus, medial part of the auditory canal Eustachian tube, corniculate and cuneiform laryneal cartilages, and the epiglottis. It contains elastic fiber networks and collagen type II fibers. The principal protein is elastin.

<span class="mw-page-title-main">Chondrocyte</span> Cell that composes cartilage

Chondrocytes are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans. Although the word chondroblast is commonly used to describe an immature chondrocyte, the term is imprecise, since the progenitor of chondrocytes can differentiate into various cell types, including osteoblasts.

<span class="mw-page-title-main">Endochondral ossification</span> Cartilaginous bone development that forms the long bones

Endochondral ossification is one of the two essential pathways by which bone tissue is produced during fetal development of the mammalian skeletal system, the other pathway being intramembranous ossification. Both endochondral and intramembranous processes initiate from a precursor mesenchymal tissue, but their transformations into bone are different. In intramembranous ossification, mesenchymal tissue is directly converted into bone. On the other hand, endochondral ossification starts with mesenchymal tissue turning into an intermediate cartilage stage, which is eventually substituted by bone.

<span class="mw-page-title-main">Mechanotransduction</span> Conversion of mechanical stimulus of a cell into electrochemical activity

In cellular biology, mechanotransduction is any of various mechanisms by which cells convert mechanical stimulus into electrochemical activity. This form of sensory transduction is responsible for a number of senses and physiological processes in the body, including proprioception, touch, balance, and hearing. The basic mechanism of mechanotransduction involves converting mechanical signals into electrical or chemical signals.

Chondropathy refers to a disease of the cartilage. It is frequently divided into 5 grades, with 0-2 defined as normal and 3-4 defined as diseased.

<span class="mw-page-title-main">Chondroblast</span> Mesenchymal progenitor cell that forms a chondrocyte

Chondroblasts, or perichondrial cells, is the name given to mesenchymal progenitor cells in situ which, from endochondral ossification, will form chondrocytes in the growing cartilage matrix. Another name for them is subchondral cortico-spongious progenitors. They have euchromatic nuclei and stain by basic dyes.

<span class="mw-page-title-main">Chondrogenesis</span>

Chondrogenesis is the biological process through which cartilage tissue is formed and developed. This intricate and tightly regulated cellular differentiation pathway plays a crucial role in skeletal development, as cartilage serves as a fundamental component of the embryonic skeleton. The term "chondrogenesis" is derived from the Greek words "chondros," meaning cartilage, and "genesis," meaning origin or formation.

Articular cartilage, most notably that which is found in the knee joint, is generally characterized by very low friction, high wear resistance, and poor regenerative qualities. It is responsible for much of the compressive resistance and load bearing qualities of the knee joint and, without it, walking is painful to impossible. Osteoarthritis is a common condition of cartilage failure that can lead to limited range of motion, bone damage and invariably, pain. Due to a combination of acute stress and chronic fatigue, osteoarthritis directly manifests itself in a wearing away of the articular surface and, in extreme cases, bone can be exposed in the joint. Some additional examples of cartilage failure mechanisms include cellular matrix linkage rupture, chondrocyte protein synthesis inhibition, and chondrocyte apoptosis. There are several different repair options available for cartilage damage or failure.

<span class="mw-page-title-main">Aggrecan</span>

Aggrecan (ACAN), also known as cartilage-specific proteoglycan core protein (CSPCP) or chondroitin sulfate proteoglycan 1, is a protein that in humans is encoded by the ACAN gene. This gene is a member of the lectican (chondroitin sulfate proteoglycan) family. The encoded protein is an integral part of the extracellular matrix in cartilagenous tissue and it withstands compression in cartilage.

<span class="mw-page-title-main">Proteoglycan 4</span> Proteoglycan; lubricant; gene

Proteoglycan 4 or lubricin is a proteoglycan that in humans is encoded by the PRG4 gene. It acts as a joint/boundary lubricant.

<span class="mw-page-title-main">Matrilin-3</span> Protein-coding gene in the species Homo sapiens

Matrilin-3 is a protein that in humans is encoded by the MATN3 gene. It is linked to the development of many types of cartilage, and part of the Matrilin family, which includes Matrilin-1, Matrilin-2, Matrilin-3, and Matrilin-4, a family of filamentous-forming adapter oligomeric extracellular proteins that are linked to the formation of cartilage and bone, as well as maintaining homeostasis after development. It is considered an extracellular matrix protein that functions as an adapter protein where the Matrilin-3 subunit can form both homo-tetramers and hetero-oligomers with subunits from Matrilin-1 which is the cartilage matrix protein. This restricted tissue has been strongly expressed in growing skeletal tissue as well as cartilage and bone.

Articular cartilage repair treatment involves the repair of the surface of the articular joint's hyaline cartilage, though these solutions do not perfectly restore the articular cartilage. These treatments have been shown to have positive results for patients who have articular cartilage damage. They can provide some measure of pain relief, while slowing down the accumulation of damage, or delaying the need for joint replacement surgery.

Mechanobiology is an emerging field of science at the interface of biology, engineering, chemistry and physics. It focuses on how physical forces and changes in the mechanical properties of cells and tissues contribute to development, cell differentiation, physiology, and disease. Mechanical forces are experienced and may be interpreted to give biological responses in cells. The movement of joints, compressive loads on the cartilage and bone during exercise, and shear pressure on the blood vessel during blood circulation are all examples of mechanical forces in human tissues. A major challenge in the field is understanding mechanotransduction—the molecular mechanisms by which cells sense and respond to mechanical signals. While medicine has typically looked for the genetic and biochemical basis of disease, advances in mechanobiology suggest that changes in cell mechanics, extracellular matrix structure, or mechanotransduction may contribute to the development of many diseases, including atherosclerosis, fibrosis, asthma, osteoporosis, heart failure, and cancer. There is also a strong mechanical basis for many generalized medical disabilities, such as lower back pain, foot and postural injury, deformity, and irritable bowel syndrome.

Cartilage repair techniques are the current focus of large amounts of research. Many different strategies have been proposed as solutions for cartilage defects. Surgical techniques currently being studied include:

Gene therapy for osteoarthritis is the application of gene therapy to treat osteoarthritis (OA). Unlike pharmacological treatments which are administered locally or systemically as a series of interventions, gene therapy aims to establish sustained therapeutic effect after a single, local injection.

Alpha collagen is specifically designed to deliver specific ratios of α- chain peptides as building blocks. The targeted cells can process the α- chain peptides to form triple helix collagen, and replenish the collagen in the targeted site. Scientists believe that Alpha collagen can help to deliver specific ratios of peptides to benefit the targeted cells.

Nasal chondrocytes (NC) are present in the hyaline cartilage of the nasal septum and in fact are the only cell type within the tissue. Similar to chondrocytes present in articular cartilage, NC express extracellular matrix proteins such as glycosaminoglycans and collagen.

Artificial cartilage is a synthetic material made of hydrogels or polymers that aims to mimic the functional properties of natural cartilage in the human body. Tissue engineering principles are used in order to create a non-degradable and biocompatible material that can replace cartilage. While creating a useful synthetic cartilage material, certain challenges need to be overcome. First, cartilage is an avascular structure in the body and therefore does not repair itself. This creates issues in regeneration of the tissue. Synthetic cartilage also needs to be stably attached to its underlying surface i.e. the bone. Lastly, in the case of creating synthetic cartilage to be used in joint spaces, high mechanical strength under compression needs to be an intrinsic property of the material.

References

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  13. 1 2 Korhonen, R. K.; Laasanen, M. S.; Töyräs, J.; Rieppo, J.; Hirvonen, J.; Helminen, H. J.; Jurvelin, J. S. (2002). "Comparison of the Equilibrium Response of Articular Cartilage in Unconfined Compression, Confined Compression and Indentation". Journal of Biomechanics. 35 (7): 903–909. doi:10.1016/S0021-9290(02)00052-0. PMID   12052392.
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  20. ↑ "Osteoarthritis". Mayo Clinic. Retrieved 13 May 2024.
  21. ↑ Rhee DK, Marcelino J, Baker M, Gong Y, Smits P, Lefebvre V, et al. (March 2005). "The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth". The Journal of Clinical Investigation. 115 (3): 622–31. doi:10.1172/JCI22263. PMC   548698 . PMID   15719068.
  22. ↑ Klabukov, I.; Atiakshin, D.; Kogan, E.; Ignatyuk, M.; Krasheninnikov, M.; Zharkov, N.; Yakimova, A.; Grinevich, V.; Pryanikov, P.; Parshin, V.; Sosin, D.; Kostin, A.A.; Shegay, P.; Kaprin, A.D.; Baranovskii, D. (2023). "Post-Implantation Inflammatory Responses to Xenogeneic Tissue-Engineered Cartilage Implanted in Rabbit Trachea: The Role of Cultured Chondrocytes in the Modification of Inflammation". International Journal of Molecular Sciences. 24 (23): 16783. doi: 10.3390/ijms242316783 . ISSN   1422-0067. PMC   10706106 . PMID   38069106.
  23. ↑ International Cartilage Repair Society ICRS
  24. 1 2 Adelnia, Hossein; Ensandoost, Reza; Shebbrin Moonshi, Shehzahdi; Gavgani, Jaber Nasrollah; Vasafi, Emad Izadi; Ta, Hang Thu (2022-02-05). "Freeze/thawed polyvinyl alcohol hydrogels: Present, past and future". European Polymer Journal. 164: 110974. Bibcode:2022EurPJ.16410974A. doi:10.1016/j.eurpolymj.2021.110974. hdl: 10072/417476 . ISSN   0014-3057. S2CID   245576810.
  25. ↑ "Supplements for osteoarthritis 'do not work'". BBC News. 16 September 2010.
  26. ↑ Ansari, Mohammad Y.; Ahmad, Nashrah; Haqqi, Tariq M. (2018-09-05). "Butein Activates Autophagy Through AMPK/TSC2/ULK1/mTOR Pathway to Inhibit IL-6 Expression in IL-1β Stimulated Human Chondrocytes". Cellular Physiology and Biochemistry. 49 (3): 932–946. doi: 10.1159/000493225 . ISSN   1015-8987. PMID   30184535. S2CID   52166938.
  27. ↑ Osteoarthritis Archived 2011-07-07 at the Wayback Machine . Osteoarthritis.about.com. Retrieved on 2015-10-26.
  28. 1 2 3 4 Cole AG, Hall BK (2004). "The nature and significance of invertebrate cartilages revisited: distribution and histology of cartilage and cartilage-like tissues within the Metazoa". Zoology. 107 (4): 261–73. Bibcode:2004Zool..107..261C. doi:10.1016/j.zool.2004.05.001. PMID   16351944.
  29. 1 2 Tarazona OA, Slota LA, Lopez DH, Zhang G, Cohn MJ (May 2016). "The genetic program for cartilage development has deep homology within Bilateria". Nature. 533 (7601): 86–9. Bibcode:2016Natur.533...86T. doi:10.1038/nature17398. PMID   27111511. S2CID   3932905.
  30. ↑ Eflora – Glossary. University of Sydney (2010-06-16). Retrieved on 2015-10-26.

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