Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China; Department of Orthopaedics, Chengdu Military General Hospital, Chengdu, Sichuan Province, China.
Department of Orthopaedics, Chengdu Military General Hospital, Chengdu, Sichuan Province, China.
Biochem Biophys Res Commun. 2014 Jun 6;448(3):241-7. doi: 10.1016/j.bbrc.2014.04.091. Epub 2014 May 2.
Differentiation-specific microRNAs may play a critical role in MSC differentiation, and they can be altered by PDGF signaling. We propose that PDGF modulates MSC differentiation by regulating microRNA expression. Therefore, we investigated whether PDGF treatment could alter the expression profile of miRNAs in MSCs. Furthermore, we assessed the osteoblast phenotype of MSCs after inducing osteogenic differentiation. We found that PDGF treatment significantly inhibits the osteogenic differentiation of MSCs and that miR-138 gene transcription is controlled by PDGF signaling. Our results confirm that miR-138 inhibits the osteogenic differentiation of MSCs and suppresses the phosphorylation of FAK, ERK1/2, and Runx2. Furthermore, our study clearly demonstrates that downregulation of Runx2 by miR-138 is critical for the PDGF-mediated inhibition of osteogenic differentiation of MSCs. These findings indicate that inhibition of miR-138 function in MSCs, either by treatment with anti-miR-138 or by overexpression of the miR-138 target sequence (miRNA sponge), could represent a potential therapeutic strategy for the treatment of bone homeostasis disorders caused by activation of the PDGF pathway.
分化特异性 microRNAs 可能在 MSC 分化中发挥关键作用，并且它们可以被 PDGF 信号改变。我们提出 PDGF 通过调节 microRNA 表达来调节 MSC 分化。因此，我们研究了 PDGF 处理是否可以改变 MSC 中 microRNA 表达谱。此外，我们评估了诱导成骨分化后 MSC 的成骨表型。我们发现 PDGF 处理显著抑制 MSC 的成骨分化，并且 miR-138 基因转录受 PDGF 信号的控制。我们的结果证实 miR-138 抑制 MSC 的成骨分化，并抑制 FAK、ERK1/2 和 Runx2 的磷酸化。此外，我们的研究清楚地表明，miR-138 下调 Runx2 对于 PDGF 介导的 MSC 成骨分化抑制至关重要。这些发现表明，抑制 MSC 中 miR-138 的功能，无论是通过用抗 miR-138 处理还是过表达 miR-138 的靶序列（miRNA 海绵），都可能代表治疗由 PDGF 途径激活引起的骨稳态紊乱的潜在治疗策略。
