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Updated: Aug 17 2024

Articular Cartilage

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  • forms of cartilage
    • Articular cartilage is one of five forms of cartilage
      • hyaline or articular cartilage
      • fibroelastic cartilage (meniscus)
      • fibrocartilage (at tendon and ligament insertion into bone)
      • elastic cartilage (trachea)
      • physeal cartilage (growth plate)
  • Articular (hyaline) Cartilage Components
    • Function
      • decreases friction and distributes loads
      • cartilage exhibits stress-shielding of the solid matrix components due to its high water content, the incompressibility of water, and the structural organization of the proteoglycan and collagen molecules
    • Composition
      • includes
        • extracellular matrix (water, collagen, proteoglycans)
        • 90% type II collagen
        • cells (chondrocytes)
      • % by weight
        • water > collagen > proteoglycan > noncollagenous protein > cells
    • Extracellular matrix
      • water
        • makes up 65% to 80% of mass of the cartilage
          • accounts for 80% of the weight near the surface
          • 65% at the deep zone
        • water content
          • decreases with normal aging
          • increases with osteoarthritis
            • increased water content leads to
              • increased permeability
              • decreased strength
              • decreased Young Modulus of elasticity
      • collagen
        • makes up 10 to 20% of total cartilage mass
        • type II collagen accounting for 90% to 95% of the total collagen content.
          • functions to provide cartilagenous framework and tensile strength
        • small amounts of types V, VI, IX, X, and XI collagen are also present
      • proteoglycans
        • make up 10 to 15% of cartilage
        • function to provide compressive strength and attract water
        • aggrecan is most responsible for hydrophilic behavior
          • content increases in early stages of OA, decreases in late OA 
        • produced by chondrocytes
        • proteoglycans composed of GAG subunits
          • chondroitin sulfate
          • keratin sulfate
      • noncollagenous protein
    • Cells
      • chondrocytes
        • produce collagen, proteoglycans, and enzymes
        • derive from chondroblasts that are trapped in lacunae and become chondrocytes
        • chondrocyte metabolism responds to both mechanical (mechanical load, hydrostatic pressure change) and chemical stimuli (growth factors, cytokines)
        • immature articular cartilage has stem cells (mature articular cartilage does not)
  • Layers of Articular Cartilage
    • Normal articular cartilage is composed of three zones and the tidemark
      • zones based on the shape of the chondrocytes and the orientation of the type II collagen.
      • Zones of Articular Cartilage
      • (tangential zone)
      • Type II collagen orientation is parallel to joint
      • Has flattened chondrocytes, condensed collagen fibers, and sparse proteoglycans
      • Has the highest concentration of collagen and lowest concentration of proteoglycans
      • Only zone where articular cartilage progenitor cells have been found
      • Intermediate zone
      • Type II collagen has an oblique or random organization
      • Is the thickest layer with round chondrocytes, and abundant proteoglycan content
      • Deep layer
      • (basal layer)
      • Type II collagen is perpendicular to joint and crosses tidemark
      • Has the highest concentration of proteoglycans
      • Round chondrocytes arranged in columns
      • Tidemark
      • Is deep to the basal layer and separates the true articular cartilage from the deeper cartilage that is a remnant of the cartilage anlage, which participated in endochondral ossification during longitudinal growth in childhood.
      • The tidemark divides
      •      - the superficial, uncalcified cartilage from the deeper, calcified cartilage
      •      - division between nutritional sources for the chondrocytes
      • The tidemark is found only in joints
      • Most prominently in the adult and nongrowing joint
      • Subchondral Bone
  • Growth Factors
    • PDGF
      • thought to be involved with healing of articular cartilage lacerations
      • effects extrapolated from PRP (which contains it)
      • no adverse effects in normal joints
    • TGF-B
      • stimulates proteoglycan and ECM synthesis
      • decreases catabolic activity of IL-1 and MMPs
      • causes synovial proliferation and fibrosis
      • induces osteophyte formation
    • b-FGF (Basic Fibroblastic Growth Factor)
      • stimulates DNA synthesis in articular chondrocytes
    • IGF-1 (Insulin growth factor -1)
      • stimulates DNA and cartilage matrix synthesis in adult articular cartilage
      • stimulates ECM synthesis
      • decreaes synovial thickening and chronic synovial inflammation
      • additive when combined with TGF-b
  • Nourishment and Metabolism
    • Cartilage is avascular
    • Nourished by
      • synovial fluid at the surface
      • subchondral bone at the base
    • Relies on glycolysis for ATP production
  • Mechanical Stress Response
    • Physiologic stress stimulates matrix synthesis and inhibits chondrolysis
      • cyclic stress (1-5 MPa)
      • moderate frequency (0.1-1 Hz)
      • low rates (<1000 MPa/s)
    • Excess stress suppresses matrix synthesis and promotes chondrolysis
      • excess stress (>5 MPa)
      • static load (<0.01 Hz)
      • high rates (>1000 MPa/s)
    • Cellular responses
      • primary cilia act as a mechanosensory organ on chondrocytes and osteoblasts
      • transduction of mechanical signals involves integrins
    • Repetitive loading
      • moderate running increases cartilage thickness and proteoglycan content
      • strenuous loading leads to cartilage thinning and proteoglycan loss
      • immobilization leads to cartilage thinning, softening and proteoglycan loss
  • Wear Mechanics
    • Forms of lubrication
      • elastohydrodynamic
        • main mechanism during dynamic joint function
        • elastic deformation of articular surfaces
        • thin films of lubricant separate the surfaces
        • a fully congruent joint will not allow a fluid film to form
      • boundary (slippery surfaces)
        • bearing surface is non-deformable
        • lubricant only partially separates surfaces
        • superficial zone proteins have a role in this lubrication mechanism
      • boosted (fluid entrapment)
        • concentration of lubricating fluid in pools
        • trapped by regions of bearing surfaces that are making contact
      • hydrodynamic
        • fluid separates surfaces when one surface is sliding on the other
      • weeping
        • fluid shifts out of articular cartilage in response to load
        • surfaces separated by hydrostatic pressure
    • Mechanisms of wear
      • adhesion
      • abrasion
      • transfer
      • fatigue
      • third body
  • Aging in Articular Cartilage
    • With age changes in articular cartilage include
      • increases in
        • chondrocytes size
        • protein content
        • stiffness (passive glycation leads to increased stiffness of collagen)
        • increase in ratio of proteoglycan keratin sulfate to chondroitin sulfate
      • decrease in
        • absolute number of cells (becomes hypocellular, despite the fact that individual chondrocytes are increasing in size)
        • water content (differentiates from osteoarthritis where water content actually increases)
        • solubility
        • proteoglycan size
        • elasticity
    • Advanced glycosylation end-products (AGEs)
      • from spontaneous nonenzymatic glycation of proteins when sugars (glucose, fructose, ribose) react with lysine or arginine residues
      • because of the low turnover, articular cartilage is susceptible to AGEs accumulation.
      • accumulation of AGEs has been thought to play a role in the development of OA of the knee and ankle.
      • effects of AGEs formation
        • modification of type II collagen by cross-linking of collagen molecules
          • increasing stiffness and brittleness
          • increasing susceptibility to fatigue failure
      • Aging vs. Osteoarthritis effect on Articular Cartilage
      • Aging
      • Osteoarthritis
      • Water
      • Decreased
      • Modulus/stiffness
      • Increased (less elastic)
      • Decreased (more elastic)
      • Chondrocytes
      • Fewer but increased size
      • Cells cluster (late stage)
      • Glycosaminoglycans
      • Increased keratan sulfate:chondroitin 4 sulfate ratio, constant chondroitin 6 sulfate
      • Increased chondroitin 4 sulfate:keratan sulfate ratio
      • Proteoglycans
      • Increased decorin, decreased proteoglycan size
      • Proteoglycans unbound from hyaluronate
      • Collagen
      • Increased collagen crosslinking/brittleness
      • Collagen disorganized (increased collagenase)
      • Advanced Glycosylation End products (AGE)
      • Increased
      • Accumulation of AGE thought to lead to OA knee and ankle
    • Injury
      • Following an intra-articular fracture, in addition to mechanical disruption and cartilage necrosis, the following inflammatory cytokines are released, contributing to articular damage and the eventual development of post-traumatic arthritis:IL-1β, TNF-α, nitric oxide, matrix metalloproteinases, aggrecans, and damage associated molecular patterns.
        • Predominant pathway of chondrocyte death believed to be via apoptosis (versus necrotic) 
  • Healing in Articular Cartilage
    • Deep lacerations (through tidemark)
      • leads to fibrocartilage healing
      • occurs when laceration travels through tidemark and penetrates subchondral bone
      • fibrocartilage produced by undifferentiated marrow mesenchymal stem cells
      • a healing response is initiated with hematoma, stem cell migration, and vascular ingrowth.
      • This response produces type I collagen and resultant fibrocartilage rather than desired hyaline cartilage as produced by chondrocytes.
      • This repair cartilage has diminished resiliency, stiffness, poor wear characteristics, and the predilection for arthritis.
    • Superficial laceration (not through tidemark)
      • leads to chondrocytes proliferation but no healing takes place because of avascular nature of cartilage
  • Clinical Conditions
    • Articular Defects of the Knee (Adults)
    • Osteocondritis dissecans
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