Cyclooxygenase inhibitors augment the production of pro‐matrix metalloproteinase 9 (progelatinase B) in rabbit articular chondrocytes

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Abstract
Matrix metalloproteinase 9 (MMP‐9/gelatinase B) has recently been proposed to participate in the destruction of articular cartilage. Here, we report that interleukin 1 (IL‐1) enhances the production of the precursor of MMP‐9 in rabbit articular chondrocytes in primary culture, and this IL‐1‐mediated production of proMMP‐9 is greatly augmented by cyclooxygenase inhibitors such as diclofenac and indomethacin, whereas the constitutive production of proMMP‐2 (progelatinase A) is not modulated by IL‐1 and/or cyclooxygenase inhibitors. Exogenous prostaglandin (PG) E1 and PGE2 suppress the proMMP‐9 production in a dose‐dependent manner. Similar results are also obtained with cultured rabbit synoviocytes. These results provide the first evidence that PGE down‐regulates the production of proMMP‐9 in chondrocytes and synoviocytes. Thus, cyclooxygenase inhibitors probably exert undesirable catabolic actions on the maintenance of articular cartilage under inflammatory conditions.