As the matrix is resorbed by hypertrophic cells, type II collagen is denatured (Alini et al 1992). This can be measured immunologically using an antibody to an intrachain epitope (Dodge & Poole 1989). The principle proteinases that can cleave type II collagen belong to the matrix metalloproteinase (MMP) family and are called collagenases. There are three such enzymes namely collagenase 1 (MMP1 or interstitial collagenase), collagenase 2 (MMP8 or neutrophil collagenase), and collagenase 3 (MMP13). Of these three collagenases, MMP13 is most effective at cleaving type II collagen (see Billinghurst et al 1997). There is another proteinase called membrane type I-MMP (MT1-MMP or MMP14) which has been reported to cleave this collagen and activate MMP13. MMP14 and MMP8 have not been detected in the growth plate. However, a null mutation for MMP14 does not exhibit any lack of collagen II cleavage or matrix resorption in the growth plate (Holmbeck et al 1999, Poole et al 2000) although cleavage of type II collagen in other tissues is inhibited. These collagenases cleave the triple helix at a point approximately three quarters distant from the N-terminus. Following cleavage and denaturation, the a chains are susceptible to cleavage by a wide variety of MMPs. The collagen fibril can also be cleaved in the telopeptide domain (Poole 1997) but as yet there is no published evidence that this occurs in situ.
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