Division of Organ Transplantation, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Division of Organ Transplantation, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
Mol Med Rep. 2018 May;17(5):6301-6310. doi: 10.3892/mmr.2018.8713. Epub 2018 Mar 9.
Postmenopausal osteoporosis (OPM) is a common type of osteoporosis in females. It is a systemic, chronic bone disease that presents as microstructure degradation of osseous tissue, decreased bone mineral density and increased osteopsathyrosis caused by hypoovarianism and reduced estrogen levels in the body following menopause. In the present study, the role of microRNA (miR)‑214‑5p in the regulation of the expression of bone marrow stem cells (BMSCs) was investigated, and its molecular mechanism of osteogenic induction in vitro was assessed. When dexamethasone‑induced adipogenic differentiation was performed, miR‑214‑5p expression was increased compared with the control group, as determined by RT‑qPCR. Furthermore, oil red O staining, RT‑qPCR and western blot analysis demonstrated that overexpression of miR‑214‑5p promoted adipogenic differentiation, inhibited alkaline phosphatase (ALP), runt‑related transcription factor 2 (Runx2), osteocalcin (OC) and collagen α‑1 (I) chain (COL1A1) mRNA expression, and suppressed transforming growth factor (TGF)‑β, phosphorylated (p)‑Smad2 and collagen type IV α1 chain (COL4A1) protein expression in BMSCs. Additionally, downregulation of miR‑214‑5p increased the ALP, Runx2, OC and COL1 mRNA expression and increased TGF‑β, Smad2 and COL4A1 protein expression in BMSCs. Furthermore, a TGF‑β inhibitor was employed to inhibit TGF‑β expression in BMSCs following miR‑214‑5p downregulation, which led to reduced Smad2, TGF‑β and COL4A1 protein expression, and ALP, Runx2, OC and COL1 mRNA expression was also reduced, compared with the miR‑214‑5p downregulation only group. It was demonstrated that miR‑214‑5p may weaken osteogenic differentiation of BMSCs through regulating COL4A1. In conclusion, the results of the present study indicated that miR‑214‑5p may promote the adipogenic differentiation of BMSCs through regulation of the TGF‑β/Smad2/COL4A1 signaling pathway, and potentially may be used to develop a novel drug for postmenopausal osteoporosis.
绝经后骨质疏松症（OPM）是女性中常见的一种骨质疏松症。它是一种全身性、慢性骨骼疾病，表现为骨骼组织的微观结构降解、骨矿物质密度降低和骨质减少，其病因是由于卵巢功能下降和绝经后体内雌激素水平降低。本研究旨在探讨微小 RNA（miR）-214-5p 在调节骨髓间充质干细胞（BMSCs）表达中的作用，并评估其在体外成骨诱导的分子机制。当使用地塞米松诱导脂肪分化时，与对照组相比，miR-214-5p 的表达增加，这是通过 RT-qPCR 确定的。此外，油红 O 染色、RT-qPCR 和 Western blot 分析表明，miR-214-5p 的过表达促进了脂肪分化，抑制碱性磷酸酶（ALP）、 runt 相关转录因子 2（Runx2）、骨钙素（OC）和胶原 α-1（I）链（COL1A1）mRNA 的表达，并抑制转化生长因子（TGF）-β、磷酸化（p）-Smad2 和胶原类型 IV α1 链（COL4A1）蛋白的表达在 BMSCs 中。此外，下调 miR-214-5p 增加了 BMSCs 中的 ALP、Runx2、OC 和 COL1 mRNA 表达，并增加了 TGF-β、Smad2 和 COL4A1 蛋白表达。此外，在下调 miR-214-5p 后，使用 TGF-β 抑制剂抑制 BMSCs 中的 TGF-β 表达，导致 Smad2、TGF-β 和 COL4A1 蛋白表达减少，同时 ALP、Runx2、OC 和 COL1 mRNA 表达也减少，与仅下调 miR-214-5p 组相比。结果表明，miR-214-5p 可能通过调节 COL4A1 来削弱 BMSCs 的成骨分化。综上所述，本研究结果表明，miR-214-5p 可能通过调节 TGF-β/Smad2/COL4A1 信号通路促进 BMSCs 的脂肪分化，并可能用于开发治疗绝经后骨质疏松症的新药。
