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首页> 外文期刊>Cell and Tissue Research >Oncostatin M regulates osteogenic differentiation of murine adipose-derived mesenchymal progenitor cells through a PKCdelta-dependent mechanism
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Oncostatin M regulates osteogenic differentiation of murine adipose-derived mesenchymal progenitor cells through a PKCdelta-dependent mechanism

机译:抑癌素M通过PKCdelta依赖性机制调节鼠源性间充质祖细胞的成骨分化

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摘要

Oncostatin M (OSM) is an IL-6/LIF family cytokine that influences mesenchymal progenitor differentiation; however, the mechanisms of this activity have not been fully elucidated. Using uncommitted murine adipose tissue-derived mesenchymal progenitors, we have examined mechanisms of OSM-induced osteogenesis. Murine OSM (mOSM) induced osteogenic differentiation to a greater degree than interleukin (IL)-6 and other members of the gp130 cytokine family, promoting extracellular matrix mineralization as indicated by Alizarin Red S staining. mOSM also increased expression of osteogenesis-associated gene products BMP4, BMP7, Runx-2, and osteocalcin as assessed by immunoblotting and real-time quantitative PCR. Additionally, protein kinase C (PKC) delta activity was upregulated in response to OSM stimulation, and to a greater degree than IL-6. Knockdown of PKCdelta expression by use of RNA interference (RNAi) reduced OSM-mediated osteogenic differentiation and decreased expression of Runx-2. These findings suggest that OSM differentially promotes osteogenesis in non-committed mesenchymal progenitors relative to other gp130 cytokines. This activity correlates with selective activation of PKCdelta in OSM-treated cells, indicating that OSM-induced osteogenesis and upregulation of osteogenic gene products require activity of PKCdelta.
机译:癌抑素M(OSM)是一种IL-6 / LIF家族细胞因子,可影响间充质祖细胞的分化。但是,这种活动的机制尚未完全阐明。我们使用未承诺的鼠类脂肪组织来源的间充质祖细胞,研究了OSM诱导成骨的机制。鼠OSM(mOSM)比白介素(IL)-6和gp130细胞因子家族的其他成员更大程度地诱导成骨分化,如茜素红S染色所示,可促进细胞外基质矿化。通过免疫印迹和实时定量PCR评估,mOSM还增加了与成骨相关的基因产物BMP4,BMP7,Runx-2和骨钙素的表达。另外,响应于OSM刺激,蛋白激酶C(PKC)δ活性被上调,并且其程度高于IL-6。使用RNA干扰(RNAi)抑制PKCdelta表达减少OSM介导的成骨分化和Runx-2的表达减少。这些发现表明,相对于其他gp130细胞因子,OSM在非定型的间充质祖细胞中差异地促进成骨作用。此活性与OSM处理的细胞中PKCdelta的选择性激活相关,表明OSM诱导的成骨和成骨基因产物的上调需要PKCdelta的活性。

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