Runx1 is critical for PTH-induced onset of mesenchymal progenitor cell chondrogenic differentiation.

Runx1 is critical for PTH-induced onset of mesenchymal progenitor cell chondrogenic differentiation.
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Runx1 对于 PTH 诱导间充质祖细胞软骨分化的发生至关重要

DOI:
10.1371/journal.pone.0074255
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Dong Y
Dong Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wang J;Wang X;Holz JD;Rutkowski T;Wang Y;Zhu Z;Dong Y

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甲状旁腺激素(PTH)在软骨形成的调节中起着关键作用。在这项研究中,我们首次发现Runt相关转录因子1(Runx1)有助于PTH诱导的软骨形成。在PTH治疗后,肢芽间充质祖细胞在微团培养中显示出增强的软骨形成,这与软骨形成标记基因表达的显著增加相关,如II型胶原和X型胶原。Runx1也只在软骨形成的起始阶段用PTH处理的细胞中表达。Runx1的敲除完全减弱了PTH介导的软骨形成。此外,PTH诱导Runx1的表达和软骨形成显着减少蛋白激酶A(PKA)信号的抑制。综上所述,我们目前的研究表明,在间充质祖细胞中PTH诱导的软骨形成是由Runx1介导的,这涉及PKA的激活。这些数据为理解PTH增强软骨再生背后的分子机制提供了新的见解。
Parathyroid hormone (PTH) plays a critical role in the regulation of chondrogenesis. In this study, we have found for the first time that Runt-related transcription factor 1 (Runx1) contributes to PTH-induced chondrogenesis. Upon PTH treatment, limb bud mesenchymal progenitor cells in micromass culture showed an enhanced chondrogenesis, which was associated with a significant increase of chondrogenic marker gene expression, such as type II collagen and type X collagen. Runx1 was also exclusively expressed in cells treated with PTH at the onset stage of chondrogenesis. Knockdown of Runx1 completely blunted PTH-mediated chondrogenesis. Furthermore, PTH induced Runx1 expression and chondrogenesis were markedly reduced by inhibition of protein kinase A (PKA) signaling. Taken together, our present study indicates that chondrogenesis induced by PTH in mesenchymal progenitor cells is mediated by Runx1, which involves the activation of PKA. These data provide a novel insight into understanding the molecular mechanisms behind PTH-enhanced cartilage regeneration.
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