TUMOUR NECROSIS FACTOR-α UP-REGULATES THE EXPRESSION OF BMP-4 mRNA BUT INHIBITS CHONDROGENESIS IN MOUSE CLONAL CHONDROGENIC EC CELLS, ATDC5

Abstract

Tumour necrosis factor (TNF)-α causes the degradation of articular cartilage in arthritis via direct actions on chondrocytes. However, it remains unknown whether TNF-α affects chondrogenesis in chondroprogenitors. In the present study, we assessed the effects of TNF-α in vitro on chondrogenesis using mouse clonal chondrogenic EC cells, ATDC5. TNF-α (10ng/ml) stimulated [3H] thymidine incorporation in undifferentiated ATDC5 cells, and suppressed cartilaginous nodule formation and the accumulation of cartilage-specific proteoglycan. We recently showed that undifferentiated ATDC5 cells express BMP-4 and that exogenously administered BMP-4 promotes chondrogenesis in these cells. Interestingly, TNF-α up-regulated the expression of BMP-4 mRNA in undifferentiated ATDC5 cells in time- and dose-dependent manners. However, exogenously administered BMP-4 was not capable of reversing the inhibitory action of TNF-α on chondrogenesis in ATDC5 cells. These results indicate that TNF-α stimulates both cell proliferation and BMP-4 expression but inhibits chondrogenesis in chondroprogenitor-like ATDC5 cells.