DEGRADATION OF CARTILAGE AGGRECAN BY COLLAGENASE-3 (MMP-13)

Degradation of the large cartilage proteoglycan aggrecan in arthritis involves an unidentified enzyme aggrecanase, and at least one of the m atrix metalloproteinases. Proteinase-sensitive cleavage sites in the a ggrecan interglobular domain (IGD) have been identified for many of th e human MMPs, as well as for aggrecanase and other proteinases, The ma jor MMP expressed by chondrocytes stimulated with retinoic acid to deg rade their matrix is collagenase-3 or MMP-13. Because of its potential role in aggrecan degradation we examined the specificity of MMP-13 fo r an aggrecan substrate, The results show that MMP-13 cleaves aggrecan in the IGD at the same site (..PEN(341)-FFG..) identified for other m embers of the MMP family, and also at a novel site ..VKP384-VFE.. not previously observed for other proteinases.