The effect of IL-1β on the expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in human chondrocytes

Interleukin-1 (IL-1) plays key roles in altering cartilage matrix turnover. This turnover is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs). In the present study, we examined the effect of IL-1 beta on cell proliferation, alkaline phosphatase (ALPase) activity, and the expression of MMPs, and TIMPs in chondrocytes derived from normal human femoral cartilage. The cells were cultured in Dulbecco's modified Eagle's medium containing 15% fetal bovine serum and 0, 1, 10, or 100 U/ml of IL-1 beta for up to 28 days. The level of expression of MMPs and TIMPs was estimated by determining mRNA levels using real-time PCR and by determining protein levels using an enzyme-linked immunosorbent assay. Cell proliferation decreased in the presence of IL-1 p after day 21 of culture. ALPase activity decreased significantly in the presence of IL-1 beta after day 10 of culture. The expression of MMP-1, -2, and -3 increased markedly in the presence of IL-1 beta after day 21 of culture. MMP-13 expression increased markedly in the presence of IL-1 beta p on day 1of culture, but decreased markedly after day 7. The expression of TIMP-1ncreased significantly after day 14 of culture. The expression of TIMP-2 decreased significantly on day 1, but increased significantly from day 3 to day 14 of culture. These results suggest that IL-1 beta may stimulate cartilage matrix turnover by increasing mainly MMP-13 production by the cells. (c) 2005 Elsevier Inc. All rights reserved.