Physiology 4530A/B Lecture Notes - Lecture 2: Aggrecan, Proteoglycan, Transforming Growth Factor Beta
15 Apr 2017
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Outer fibrous layer is innervated but avascular, continuous w periosteum. Inner fibrous layer produces synovial fluid which filters blood and provides lubrication (lubricin, hyaluronan) for joint movement. Superficial zone: flattened chondrocytes parallel to surf, highest conc of collagen fibrils + water. Deep zone: highest conc of proteoglycans/vertically oriented fibrils. Proteoglycans: aggrecan core + glycosaminoglycans (neg charged to attract water) Pericellular matrix: immediately surrounding chondrocyte (combined is chondron); high in proteoglycans. Anabolism: cartilage thickness, # of chondrocytes, ecm synthesis (colii, aggrecan), bmp, igf formation of osteophytes i. e. anabolic response does occur in oa as well (inappropriate endochondral ossification: osteophytes cause pain allodynia: normally nonpainful area becomes painful. Catabolism: thickness decrease, inflamm cytokines (tnf,il), enzymes (mmp13/adamts/cathepsins degrades ecm; timps antagonize proteases) e. g. adamts-mediated aggrecan degradation. Cleaves g1 and g2 domains of aggrecan, so 2 epitopes generated, 1 recognized by alpha-arg (go into synovial fluid b/c smaller) and the other by alpha-ege (remain bound to cartilage b/c bigger)
