Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada.
FEBS Lett. 2010 Jul 2;584(13):2877-82. doi: 10.1016/j.febslet.2010.04.074. Epub 2010 May 7.
We used cDNA microarray to identify transforming growth factor beta (TGF-beta) responsive target genes during osteoblast development and found that nephronectin (Npnt) is one such gene that is significantly down-regulated. Here we report the role of TGF-beta in regulating Npnt-mediated osteoblast differentiation. We found that the effect of TGF-beta on Npnt expression is associated with a change in cell morphology in a dose-dependent manner. Npnt-induced osteoblast differentiation was also inhibited by TGF-beta, which changed cell morphology from cuboidal to fibroblastic, an indication that osteoblast differentiation was disrupted. Furthermore, TGF-beta inhibited differentiation of osteoblasts transfected with various truncated Npnt constructs, suggesting that TGF-beta can exert a down-stream effect on Npnt function. Our results suggest that TGF-beta can inhibit osteoblast differentiation through various mechanisms.
我们使用 cDNA 微阵列来鉴定成骨细胞发育过程中转化生长因子β (TGF-β) 反应的靶基因，发现纤连蛋白 (Npnt) 是其中一个显著下调的基因。在这里，我们报告 TGF-β 在调节 Npnt 介导的成骨细胞分化中的作用。我们发现 TGF-β 对 Npnt 表达的影响与细胞形态的剂量依赖性变化有关。TGF-β 还抑制了 Npnt 诱导的成骨细胞分化，使细胞形态从立方状变为成纤维状，表明成骨细胞分化被破坏。此外，TGF-β 抑制了转染各种截断 Npnt 构建体的成骨细胞的分化，这表明 TGF-β 可以对 Npnt 功能发挥下游效应。我们的结果表明，TGF-β 可以通过多种机制抑制成骨细胞分化。
