Heat shock protein B7 (HSPB7), which belongs to small heat shock protein family, has been reported to be involved in diverse biological processes and diseases. However, whether HSPB7 regulates osteogenic differentiation of human adipose derived stem cells (hASCs) remains unexplored. The expression level of HSPB7 during the osteogenesis of hASCs was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. Lentivirus transfection was used to knock down or overexpress HSPB7, which enabled us to investigate the effect of HSPB7 on osteogenic differentiation of hASCs. U0126 and extracellular signal-regulated protein kinase 1/2 (ERK1/2) siRNA were used to identify the mechanism of the HSPB7/ERK1/2 axis in regulating osteogenic differentiation of hASCs. Moreover, ectopic bone formation in nude mice and osteoporosis mice model was used to investigate the effect of HSPB7 on osteogenesis in vivo. In this study, we found the expression of HSPB7 was significantly downregulated during the osteogenic differentiation of hASCs. HSPB7 knockdown remarkably promoted osteogenic differentiation of hASCs, while HSPB7 overexpression suppressed osteogenic differentiation of hASCs both in vitro and in vivo. Moreover, we discovered that the enhancing effect of HSPB7 knockdown on osteogenic differentiation was related to the activation of extracellular signal-regulated protein kinase (ERK) signaling pathway. Inhibition of ERK signaling pathway with U0126 or silencing ERK1/2 effectively blocked the stimulation of osteogenic differentiation induced by HSPB7 knockdown. Additionally, we found that HSPB7 expression was markedly increased in mouse bone marrow mesenchymal stem cells (mBMSCs) from the osteoporotic mice which suggested that HSPB7 might be utilized as a potential target in the development of effective therapeutic strategies to treat osteoporosis and other bone diseases. Taken together, these findings uncover a previously unrecognized function of HSPB7 in regulating osteogenic differentiation of hASCs, partly via the ERK signaling pathway.

中文翻译：

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HSPB7通过ERK信号通路调节人脂肪干细胞成骨分化

热休克蛋白 B7 (HSPB7) 属于小热休克蛋白家族，据报道参与多种生物过程和疾病。然而，HSPB7 是否调节人类脂肪干细胞 (hASCs) 的成骨分化仍有待探索。通过定量逆转录聚合酶链反应（qRT-PCR）和蛋白质印迹分析检查hASCs成骨过程中HSPB7的表达水平。慢病毒转染用于敲低或过表达 HSPB7，这使我们能够研究 HSPB7 对 hASCs 成骨分化的影响。U0126 和细胞外信号调节蛋白激酶 1/2 (ERK1/2) siRNA 用于鉴定 HSPB7/ERK1/2 轴在调节 hASCs 成骨分化中的机制。而且，使用裸鼠和骨质疏松小鼠模型中的异位骨形成来研究HSPB7对体内成骨的影响。在这项研究中，我们发现 HSPB7 的表达在 hASCs 的成骨分化过程中显着下调。HSPB7 敲低显着促进了 hASCs 的成骨分化，而 HSPB7 过表达抑制了体外和体内 hASCs 的成骨分化。此外，我们发现 HSPB7 敲低对成骨分化的增强作用与细胞外信号调节蛋白激酶 (ERK) 信号通路的激活有关。用 U0126 抑制 ERK 信号通路或使 ERK1/2 沉默有效地阻断了 HSPB7 敲低诱导的成骨分化的刺激。此外，我们发现 HSPB7 在来自骨质疏松小鼠的小鼠骨髓间充质干细胞 (mBMSCs) 中的表达显着增加，这表明 HSPB7 可能被用作开发治疗骨质疏松症和其他骨病的有效治疗策略的潜在靶点。总之，这些发现揭示了 HSPB7 在调节 hASCs 成骨分化中以前未被认识的功能，部分通过 ERK 信号通路。