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 Superficial zone (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 Increased 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