Horiguchi M, Akiyama H, Ito H, Shigeno C, Nakamura T
Department of Orthopaedic Surgery, Graduate School of Medicine, Sakyo, Kyoto, Japan.
Cytokine. 2000 May;12(5):526-30. doi: 10.1006/cyto.1999.0577.
Tumour necrosis factor (TNF)-alpha causes the degradation of articular cartilage in arthritis via direct actions on chondrocytes. However, it remains unknown whether TNF-alpha affects chondrogenesis in chondroprogenitors. In the present study, we assessed the effects of TNF-alpha in vitro on chondrogenesis using mouse clonal chondrogenic EC cells, ATDC5. TNF-alpha (10 ng/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-alpha 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-alpha on chondrogenesis in ATDC5 cells. These results indicate that TNF-alpha stimulates both cell proliferation and BMP-4 expression but inhibits chondrogenesis in chondroprogenitor-like ATDC5 cells.
肿瘤坏死因子（TNF）-α通过对软骨细胞的直接作用导致关节炎中关节软骨的降解。然而，TNF-α是否影响软骨祖细胞的软骨形成仍不清楚。在本研究中，我们使用小鼠克隆软骨生成EC细胞ATDC5评估了TNF-α在体外对软骨形成的影响。TNF-α（10 ng/ml）刺激未分化的ATDC5细胞掺入[3H]胸苷，并抑制软骨结节形成和软骨特异性蛋白聚糖的积累。我们最近发现未分化的ATDC5细胞表达骨形态发生蛋白（BMP）-4，并且外源性给予的BMP-4可促进这些细胞的软骨形成。有趣的是，TNF-α以时间和剂量依赖性方式上调未分化ATDC5细胞中BMP-4 mRNA的表达。然而，外源性给予的BMP-4不能逆转TNF-α对ATDC5细胞软骨形成的抑制作用。这些结果表明，TNF-α刺激细胞增殖和BMP-4表达，但抑制软骨祖细胞样ATDC5细胞的软骨形成。
