Hiyama A, Mochida J, Omi H, Serigano K, Sakai D
Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medcine, Boseidai, Isehara, Kanagawa 259-1193, Japan.
Biochem Biophys Res Commun. 2008 May 2;369(2):679-85. doi: 10.1016/j.bbrc.2008.02.087. Epub 2008 Feb 26.
The transforming growth factor-beta (TGF-beta) and the tumor necrosis factor-alpha (TNF-alpha) families are known to play important roles in intervertebral disc degeneration (IVD). However, molecular interactions between the TGF-beta and TNF-alpha signaling pathways have yet to be elucidated. The purpose of this study was to analyze the expression patterns of Smad transcription factor signaling associated with IVDs with aging and to examine the modulation of Smad signaling by TNF-alpha in IVD cells using SD rats. According to these experimental results, BMP signals in the TGF-beta family were more likely to be a key factor in IVD degeneration by aging, and it was predicted that besides the involvement of catabolic factors like MMPs and ADAMS-TS, there may be a decrease in expression of anabolic factors through cross talk of signaling between TNF-alpha and TGF-beta pathway in pathogenesis of disc degeneration.
已知转化生长因子-β(TGF-β)和肿瘤坏死因子-α(TNF-α)家族在椎间盘退变(IVD)中发挥重要作用。然而,TGF-β和TNF-α信号通路之间的分子相互作用尚未阐明。本研究的目的是分析与衰老相关的IVD中Smad转录因子信号的表达模式,并使用SD大鼠研究TNF-α对IVD细胞中Smad信号的调节作用。根据这些实验结果,TGF-β家族中的骨形态发生蛋白(BMP)信号更有可能是衰老导致IVD退变的关键因素,并且据推测,除了基质金属蛋白酶(MMPs)和含血小板解聚蛋白基序的金属蛋白酶(ADAMS-TS)等分解代谢因子的参与外,在椎间盘退变的发病机制中,通过TNF-α和TGF-β途径之间的信号串扰,合成代谢因子的表达可能会降低。