Abstract

expression of all MMPs was greater in meniscus than AC. In general MMP expression in the outer meniscus was more responsive to TNFα. TIMP-1 and -3 were generally decreased in all tissues by IL-1α and TNFα. There was more pro and active MMP-2, and pro-MMP-13 in control cultures of outer meniscus than AC or inner meniscus. Unlike AC, both meniscal zones released active MMP-13 after IL-1α and TNFα treatment, and active MMP-2 after IL-1α (inner) or both cytokines (outer). Conclusions: Aggrecan processing differed between outer versus inner meniscus, with the later being similar to AC. Aggrecan proteolysis in the outer meniscus rather than AC, may be responsible for MMP-generated neoepitopes detected in OA human knee synovial fluid. The meniscus was generally more responsive to TNFα than AC, particularly the outer zone. Expression of MMPs and ADAMTS was higher in meniscus than AC, and unlike AC active MMPs were released from meniscus. The meniscus may contribute significantly to metalloproteinase levels in the joint, and therefore to cartilage breakdown in OA. Differential regulation of MMPs and ADAMTS in the knee joint meniscus compared with AC, and between inner and outer meniscal zones has important implications in OA therapy.

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