Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan.
Biochem Biophys Res Commun. 2011 Jul 15;410(4):766-70. doi: 10.1016/j.bbrc.2011.06.048. Epub 2011 Jun 12.
POEM, also known as nephronectin, is an extracellular matrix protein considered to be a positive regulator of osteoblast differentiation. In the present study, we found that tumor necrosis factor-α (TNF-α), a key regulator of bone matrix properties and composition that also inhibits terminal osteoblast differentiation, strongly inhibited POEM expression in the mouse osteoblastic cell line MC3T3-E1. TNF-α-induced down-regulation of POEM gene expression occurred in both time- and dose-dependent manners through the nuclear factor kappa B (NF-κB) pathway. In addition, expressions of marker genes in differentiated osteoblasts were down-regulated by TNF-α in a manner consistent with our findings for POEM, while over-expression of POEM recovered TNF-α-induced inhibition of osteoblast differentiation. These results suggest that TNF-α inhibits POEM expression through the NF-κB signaling pathway and down-regulation of POEM influences the inhibition of osteoblast differentiation by TNF-α.
POEM，也被称为纤连蛋白，是一种细胞外基质蛋白，被认为是成骨细胞分化的正向调节因子。在本研究中，我们发现肿瘤坏死因子-α（TNF-α），一种调节骨基质特性和组成的关键因子，同时也抑制成骨细胞的终末分化，强烈抑制了小鼠成骨细胞系 MC3T3-E1 中 POEM 的表达。TNF-α通过核因子 kappa B（NF-κB）途径以时间和剂量依赖的方式下调 POEM 基因表达。此外，分化后的成骨细胞中的标记基因的表达也与我们发现的 POEM 一致被 TNF-α下调，而过表达 POEM 则恢复了 TNF-α 诱导的成骨细胞分化抑制。这些结果表明，TNF-α 通过 NF-κB 信号通路抑制 POEM 的表达，而 POEM 的下调影响了 TNF-α 对成骨细胞分化的抑制作用。
