Orthopaedic Surgery/Cartilage

Normal Articular Cartilage Articular cartilage of diarthrodial joints are covered by hyaline cartilage, which is in turn derived from the two words - hyalose a greek word for glass and cartilago, a latin word for gristle. It is relatively acellular and has no vascular, neural or lyphatic supply. Articular cartilage by its rubber like resiliency, functions to reduce pressure and where it covers the end of a bone, its smooth surface minimises the friction effect of shearing stresses. The cartilage of our joints derives its nutrition from the movement and contact pressure of the joint for its effect on transmitting the larger solutes from the joint fluid to the cellular matrix of the cartilage; a process which is potentiated when there is slight incongruity of the opposing joint surfaces. Chrondromalacia, the softening which heralds early osteoarthritis is present in most humans after age 40 and usually starts in non-load bearing areas.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=5706888

=Morphology of Articular Cartilage=
 * 1) Colour: Colour varies with age.
 * 2) *Children - transparent and white with a bluish tinge
 * 3) *Young adult - white and glossy
 * 4) *Middle aged - yellowish white
 * 5) *Advanced age - opaque and yellowish with brownish tinge
 * 6) Compressibility: Compressible under pressure but on removal of the deforming force, it springs back into its original shape (behaves as a shock absorber).
 * 7) *Children - highly compressible
 * 8) *Young adults - compressible but less than in a child
 * 9) *Middle aged - firmer and less compressible
 * 10) *Advanced age - less resilient and more resistant
 * 11) Thickness: Articular cartilage becomes thinner with disuse and in old age. In a given joint thickness varies from one area to another. In areas with concave surface, it is thicker at the periphery and thinner in the centre. Reverse is true for areas with convex surfaces. Thickness varies from joint to joint. It is thinnest in the interphalangeal joints and thickest in the patella.
 * 12) *Average thickness - 2-3 mm
 * 13) *Interphalangeal joint - 1 mm
 * 14) *Patella - 5-6 mm
 * 15) Surface: The surface appears smooth when viewed by naked eye. Microscopic examination particularly using electron microscope demonstrates surface undulations. The undulations entrap synovial fluid, facilitating the lubrication os the articular cartilage.
 * 16) *The most superficial layer of articular cartilage known as the lamina splendens is acellular measures 4 to 8 microns in thickness and consists of collagen, of a type more characteristic of synovium than articular cartilage.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15168182

=Composition of Articular Cartilage= The articular cartilage is made of cells called chondrocytes which are embedded in an extracellular matrix.


 * 1) Chondrocytes: This is one of the cells found in articular cartilage. It contributes very little to the total mass of the tissues. In a human adult it forms only 1% of the total volume. Chondrocytes differ in size and shape and metabolic activity depending on zones in the articular cartilage. Chondrocytres take active part in the synthesis of and turn over of the extra cellular matrix and replacement of degraded matrix and its components. Adult cartilage derives its nutrition from the synovial fluid. Nutrition to reach the chodrocytes must go through double diffusion barriers.
 * 2) *synovial tissue and synovial fluid
 * 3) *cartilage matrix - this system makes the chondrocytes manage with low concentration of oxygen, hence they depend more on anaerobic metabolism.
 * 4) Extracellular Matrix:It has two main components.
 * 5) *Tissue Fluid: Water contributes to 70-80% of the net weight of the articular cartilage. This tissue also contains gases, small proteins, metabolites and a high concentration of cations to balance the negatively charged proteoglycans.
 * 6) *Structural Macromolecules: These form 20-30% of the net weight of the tissue. They in turn consist of:
 * 7) *#Collagen: It contributes 60% of the dry weight. It has many types of collagen. Collagen types II, VI, IX and XI are predominant. The main collagen is type II accounting for 90-95%. Types II, IX and XI form cross-banded fibrils which form a tight mesh work. This provides the cartilage its tensile stiffness and strength and traps the large proteoglycan molecules to achieve cohesiveness. Type VI collagen is found immediately surrounding the chondrocytes assisting them to get attached to the matrix. Type X collagen is found mainly near the cells of calcified cartilage zone and suggests that it may have a role to play in the mineralization of the cartilage.
 * 8) *#Proteoglycans: These macromolecules are extremely important in affording the tissue its resiliency and in maintaining its water content. They have a linear protein core to which are attached at right angles long chains of polysaccharides known as glycosaminoglycans. Glycosaminoglycans found in articular cartilage include - hyaluronic acid, chondroitin-6 sulphate, chondroitin-4 sulphate, keratin sulphate and dermatan sulphate. Concentration of these molecules varies within the articular cartilage, and also with age, injury and disease of the cartilage. Among the glycosaminoglycans, chondroitin-6 sulphate is the principal one accounting for over 50% of the sugar component. Keratin sulphate is present only in trace amounts in immature cartilage but with advancing age, its concentration increases. Larger aggregating proteoglycan monomers are called aggregans and they fill up most of the interfibrillar space of the cartilage matrix contributing to 90% of the total cartilage matrix proteoglycan mass.
 * 9) *#Non-Collagenous Proteins and Glycoproteins: Glycoproteins have a protein core to which are attached a few chains of monosaccharides and polysaccharides.
 * 10) *#*Anchorin C-II helps to anchor chondrocyte surface protein to the collagen fibril
 * 11) *#*Cartilage oligomeric protein is found in the territorial matrix of the chondrocyte and has the capacity to bind to chondrocytes. It may have a value as a marker of cartilage turnover and may be useful in assessing the degree of degeneration in osteoarthritis.
 * 12) *#*Fibronectin and Tenascin may have a role in matrix organisation, cell-matrix interaction and the response of tissue in inflammatory arthritis and osteoarthritis.

=Structure of Articular Cartilage=
 * 1) Zones: The morphological changes in chondrocytes and matrix from articular surface to subchondral bone make it possible to identify four zones.
 * 2) *Zone I – Superficial or Gliding Zone: This is the thinnest of all the zones. It has two layers. The most superficial layer is called the ‘’’Lamina Splendens’’’ which is totally acellular. Apart from mechanical function this dense collagen skin probably reduces leakage of proteoglycans from the articular surface and protects it from the effect of harmful enzymes. Deep to Lamina Splendens, flattened ellipsoid shaped chondrocytes arrange themselves so that their major axes are parallel to the articular surface. Chondrocytes of this area produce more collagen than proteoglycan. Concentration of fibronectin and water are also highest in this zone. Collagen fibrils in this zone are numerous and lie parallel to the joint surface in the superficial zone and gives this zone great tensile strength and stiffness than the deeper layers. It also helps them to resist shearing forces generated during movement in the joint. Alteration in this zone may contribute to the development of osteoarthritis. The densely packed collagen fibrils may also limit the ingress of large molecules such as antibodies and the egress of large cartilage molecules. By behaving as a barrier this zone may isolate the remaining part of the cartilage from the immune system. Hence disruption of this zone may not only alter the structure and mechanical properties but may also release cartilage molecules that stimulate immune or inflammatory response.
 * 3) *Zone II – Transitional Zone: The cells in this zone are spheroidal in shape and have a higher concentration of synthetic organelles, such as endoplasmic reticulum and golgi apparatus than the cells in the deeper zones. The cells appear clumped into groups. They have the capacity to synthesise the matrix. The collagen fibrils in this zone are placed tangentially and latter when they traverse to the deeper aspect they change their orientation and lie perpendicular to the articular surface.
 * 4) *Zone III – Middle or Radial Zone: This is the broadest zone. The total thickness of the cartilage is determined by this zone. When well developed, this zone contributes to two-third of the thickness of the entire articular cartilage. Collagen fibrils of this zone have the largest diameter and the water concentration is the lowest. The collagen fibrils run parallel to each other and are situated perpendicular to the articular surface.
 * 5) *Zone IV – Calcified Zone: This is a thin zone that separates the Radial zone from the subchondral bone. The cells here are smaller and fewer but arranged in rows. In some areas the cells are totally buried in individual Calcified Sepulchers, suggesting that that they may have a very low level of metabolic activity. They may have a role to play in the development and progression of osteoarthritis.
 * 6) Tide Mark: The junction between the radial and calcified zones is distinctly visible as a basophilic line in stained preparations of articular cartilage This faint but distinct bluish line is known as the tide mark. It is not seen in developing individuals but in the adult cartilage The number of tide marks may increase with advancing age. This may signify that the calcified zone undergoes periodic extensions into the non-calcified zones of the cartilage with advancing age.
 * 7) Articular Cartilage – Bone Junction: At its base, articular cartilage is bordered by subchindral bone. However there is no structural continuity between the two of them. The cartilage tissue is keyed into irregular surface of the underlying bone like a jigsaw puzzle. The cartilage adjacent to the bone is calcified and has a similar rigidity like bone, hence the keying is rigid.
 * 8) Regions of the Matrix: Three distinct compartments can be delineated
 * 9) *Pericellular Region: This rim of pericellular matrix covers cell surface. It is rich in proteoglycans, anchorin C-II and non-fibrillar collagens such as Type VI collagen. Cytoplasmic extension from chondrocytes extend into this part of the matrix.
 * 10) *Territorial Region: Surrounding the pericellular region is the territorial matrix which encloses individual or clusters of  chondrocytes. In the radial zone it may even envelop each column of chondrocytes. It renders protection to the chondrocytes.
 * 11) *Interterritorial Region: It has the largest column of collagen fibres. Proteoglycans are embedded between their small little spaces.

=Interaction Between Chondrocytes and The Matrix= Chondrocytes and the matrix are interdependent on each other for maintenance. Chondrocytes secrete the macromolecules that make up the matrix and the matrix in turn protects the ch0ndrocytes from mechanical damage helping them to maintain their shape and phenotype. Synthesis and degradation of matrix molecules by is a process continuous throughout life. The mechanism that controls this balance is poorly understood but cytokines with catabolic and anabolic effects appear to have important roles. Matrix also acts as a signal transducer for the chondrocytes. It transmits signals that result from mechanical loading to chondrocytes. They in turn respond to these signals by altering the matrix. Experiments have shown that a persistent decreas4 in joint loading or immoboilisation of the joint decrease the concentration of proteoglycan. Resumption of the usage of joint leads to normalcy. Hence repetitive loading and movement helps a great deal in maintaining the homeostasis of articular cartilage.

=Aging and Osteoarthritis= Cyclic loading of the entire joint surface does not usually occur in the course of normal activities of daily living. The precursor lesion of osteoarthritis namely chondromalacia, or softening of the cartilage is observed to occur first in non-load bearing areas of the joint. Lacking the sustaining contact pressure which nutritionally replenishes the matrix and produces an anabolic mechanical stimulation,these infrequently loaded areas are depleted in sulfated mucopolysaccharides, thus they are less basophilic on haematoxylin eosin staining. As these nutritionally depleted areas from time to time do indeed sustain load they thereby break down,by a failure of normal remodeling processes, fibillation and progressive changes of osteoarthritis ensue. Secondary osseus changes then lead to increased joint congruity in the joint as a whole which lessens the nutrition enhancing effect of youthful slight incongruity in normally weight bearing areas.

Current research appears consistent with a hypothesis that applying load to these normally unloaded areas perhaps through a daily regimen of yoga or pilates may be a reasonable prescription for prevention of this ubiquitous degenerative process by enhancement of cartilage nutrition and anabolic mechanical stimulus through regular loading. In that cartilage has some inherent regenerative potential, a similar regimen could be helpful even once the pathologic changes have begun. Might it be that like the life forms in a tide pool, replenishment twice a day as from the rising tide may suffice to sustain our cartilage.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15952258

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12721352

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2383080

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=6493092

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7226665 

= Injury and Repair = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15577072

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14686827