Role of a LIF antagonist in LIF and OSM induced MMP-1, MMP-3, and TIMP-1 expression by primary articular chondrocytes

Cartilage degradation is mediated by matrix metalloproteinases (MMPs) and their inhibitors, tissuemetalloproteinases (TIMPs), which are transcriptionally regulated by a variety of growth factors and cytokines.The levels of various MMPs as well as TIMPs have been shown to increase in response to certaincytokines. These include leukaemia inhibitory factor (LIF) and Oncostatin M (OSM), both of which havebeen detected in the synovial fluids of patients with rheumatoid arthritis (RA). However, the role ofLIF and OSM in the regulation of various MMPs and TIMPs is still incompletely understood. The aimsof this study were to examine the effects of LIF and OSM on MMP-1, MMP-3, and TIMP-1 production.In addition, the capacity of the LIF antagonist, MH35-BD, to block LIF and OSM induced MMP expressionwas examined. Primary chondrocytes, isolated from porcine metacarpophalangeal cartilage, were culturedin the presence and absence of LIF and OSM, with and without a predetermined concentration ofthe LIF antagonist. We analysed the levels of MMP-1, MMP-3 and TIMP-1 expression using qRT-PCR,Northern blot, and ELISA assays. The results indicate that LIF and OSM increase the expression ofMMP-1, MMP-3, and TIMP-1 several fold. Furthermore their expression is reduced to basal levels inthe presence of the LIF antagonist MH35-BD.