Institute of Biomedical Engineering, West China School of Basic Medical Science and Forensic Medicine, Sichuan University, Chengdu 610041, Sichuan, P.R. China.
Laboratory of Cardiovascular Diseases, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, P.R.China.
Biosci Rep. 2019 Sep 3;39(9). doi: 10.1042/BSR20191011. Print 2019 Sep 30.
We aimed to evaluate whether applying low magnitude vibration (LMV) in early postmenopausal osteoporosis (PMO) suppresses its progression, and to investigate underlying mechanisms. Rats were randomly divided into Sham (Sham-operated), Sham+V, OVX (ovariectomized), OVX+E2 (estradiol benzoate), OVX+V (LMV at 12-20 weeks postoperatively), and OVX+Vi (LMV at 1-20 weeks postoperatively) groups. LMV was applied for 20 min once daily for 5 days weekly. V rats were loaded with LMV at 12-20 weeks postoperatively. Vi rats were loaded with LMV at 1-20 weeks postoperatively. Estradiol (E2) rats were intramuscularly injected at 12-20 weeks postoperatively once daily for 3 days. The bone mineral densities (BMDs), biomechanical properties, and histomorphological parameters of tibiae were analyzed. , rat bone marrow-derived mesenchymal stem cells (rBMSCs) were subjected to LMV for 30 min daily for 5 days, or 17β-E2 with or without 1-day pretreatment of estrogen receptor (ER) inhibitor ICI 182,780 (ICI). The mRNA and protein expresion were performed. Data showed that LMV increased BMD, bone strength, and bone mass of rats, and the effects of Vi were stronger than those of E2. , LMV up-regulated the mRNA and protein expressions of Runx2, Osx, Col I, and OCN and down-regulated PPARγ, compared with E2. The effects of both LMV and E2 on rBMSCs were inhibited by ICI. Altogether, LMV in early PMO suppresses its progression, which is associated with osteogenic differentiation of rBMSCs via up-regulation of ERα and activation of the canonical Wnt pathway. LMV may therefore be superior to E2 for the suppression of PMO progression.
我们旨在评估在早期绝经后骨质疏松症(PMO)中应用低幅度振动(LMV)是否抑制其进展,并探讨潜在机制。将大鼠随机分为 Sham(假手术)、Sham+V、OVX(卵巢切除术)、OVX+E2(苯甲酸雌二醇)、OVX+V(术后 12-20 周应用 LMV)和 OVX+Vi(术后 1-20 周应用 LMV)组。LMV 每天应用 20 分钟,每周 5 天。V 组大鼠在术后 12-20 周加载 LMV。Vi 组大鼠在术后 1-20 周加载 LMV。E2 组大鼠在术后 12-20 周每天肌肉注射一次,连续 3 天。分析胫骨的骨矿物质密度(BMD)、生物力学特性和组织形态学参数。此外,将大鼠骨髓间充质干细胞(rBMSCs)进行 LMV 处理,每天处理 30 分钟,连续 5 天,或用 17β-E2 加或不加 1 天的雌激素受体(ER)抑制剂 ICI 182,780(ICI)预处理。进行 mRNA 和蛋白表达分析。结果显示,LMV 增加了大鼠的 BMD、骨强度和骨量,且 Vi 的效果强于 E2。此外,与 E2 相比,LMV 上调了 rBMSCs 中 Runx2、Osx、Col I 和 OCN 的 mRNA 和蛋白表达,下调了 PPARγ。ICI 抑制了 LMV 和 E2 对 rBMSCs 的作用。总之,早期 PMO 中的 LMV 通过上调 ERα 和激活经典 Wnt 通路抑制 rBMSCs 的成骨分化,从而抑制其进展。因此,与 E2 相比,LMV 可能更适合抑制 PMO 的进展。