What is the normal matrix turnover of articular cartilage
In normal articular cartilage, chondrocytes rarely divide and are not renewed when they die. Chondrocytes synthesize and replace the extracellular matrix components. Proteoglycans have a faster turnover rate (t 1/2 of weeks) than collagen (t 1/2 of years). The degradation of these macromolecules is accomplished by proteolytic enzymes. MMPs, such as the secreted collagenase MMP-13 and the membrane-anchored MMP-14, are most important in collagen type II breakdown. Two aggrecanases (ADAMTS 4 and 5) are metalloproteinases that degrade aggrecan, the major proteoglycan in cartilage, between the Glu 373 and Ala 374 bond. Gelatinases (MMP-2, MMP-9) and stromelysins (MMP-3, MMP-10) further degrade the collagen and proteoglycan fragments. Cytokines such as interleukin (IL)-1, IL-6, and TNF-α can upregulate the degradative process, whereas TGF-β and insulin-like growth factor-1 have an anabolic effect on chondrocyte metabolism. Extracellular matrix proteins (fibronectin, collagen fragments, chondroadherin, and PRELP) interact with integrins or other cell surface receptors (syndecan), whereas hyaluronic acid interacts with CD44 to signal and regulate the chondrocyte’s synthesis of extracellular cartilage matrix. Assays using monoclonal antibodies to measure type II collagen and proteoglycans (keratan sulfate, COMP) in bodily fluids have been used to detect cartilage breakdown.
