We examined the effect of the inflammatory mediator interleukin-1alpha (IL-1alpha) on cell proliferation, alkaline phosphatase (ALPase) activity, and the expressions of cartilage matrix proteins, bone morphogenetic protein-2 (BMP-2), and BMP-2 receptors in human chondrosarcoma cell line OUMS-27 (chondrocytes). The cells were cultured with Dulbecco's modified Eagle's medium containing 15% fetal bovine serum with 0, 1, 10, or 100 units/ml of IL-1alpha for up to 14 days. The expressions of cartilage matrix proteins, BMP-2, and BMP-2 receptors were estimated by determining mRNA levels using semiquantitative or real-time PCR and/or by determining protein levels using Enzyme-linked immunosorbent assay. Cell proliferation was decreased after 5 days in culture with IL-1alpha. The ALPase activity was decreased significantly in the presence of IL-1alpha until day 10 of culture. The expression of type II collagen was significantly decreased after 7 days in culture with IL-1alpha. The expressions of aggrecan and link protein were significantly decreased through day 14 of culture with IL-1alpha. The expression of BMP-2 was increased at days 3, 7, and 14 of culture with IL-1alpha, while the expression of type II receptor for BMP-2 was significantly decreased in the samples. These results suggest that IL-1alpha suppresses the expression of cartilage matrix proteins through a suppression of the autocrine action of BMP-2, brought about by the decrease in BMP-2 receptor expression in chondrocytes.
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http://dx.doi.org/10.1016/j.lfs.2004.06.011 | DOI Listing |
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