Department of Orthopedic Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian 116011, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7692-7698. doi: 10.3892/mmr.2017.7543. Epub 2017 Sep 20.
The aim of the present study was to investigate the effects of mechanical stress on the osteogenic differentiation of human ligamentum flavum cells via the bone morphogenetic protein (BMP)‑Smad1 signaling pathway. Mechanical stress increased cell proliferation and induced osteogenic differentiation of human cells derived from the ossification of the ligamentum flavum (OLF). In addition, mechanical stress activated osteocalcin (OC), alkaline phosphatase (ALP) and runt‑related transcription factor 2 (RUNX‑2) mRNA expression, and suppressed Ets proto‑oncogene 1 (Ets‑1) and sex determining region Y‑box 2 (SOX‑2) mRNA expression in OLF cells. Src protein expression was suppressed by mechanical stress in human OLF cells. In addition, the protein expression levels of BMP, phosphorylated (p)‑mothers against decapentaplegic homolog‑1 (Smad1) and p‑p38‑mitogen‑activated protein kinases (p38MAPK) were increased by mechanical stress. These results demonstrate that mechanical stress effectively increases cell proliferation, promotes the osteogenic differentiation rate of OLF cells, activates OC, ALP and RUNX‑2, and suppresses Ets‑1 and SOX‑2 potentially via the BMP‑Smad1 and Src‑p38MAPK signaling pathways.
本研究旨在探讨机械应力通过骨形态发生蛋白(BMP)-Smad1 信号通路对人黄韧带骨化细胞成骨分化的影响。机械应力增加了人黄韧带骨化细胞(OLF)的细胞增殖,并诱导其成骨分化。此外,机械应力激活了 OLF 细胞中骨钙素(OC)、碱性磷酸酶(ALP)和 runt 相关转录因子 2(RUNX-2)mRNA 的表达,并抑制了 Ets 原癌基因 1(Ets-1)和性别决定区 Y 框 2(SOX-2)mRNA 的表达。机械应力抑制了人 OLF 细胞中 Src 蛋白的表达。此外,机械应力增加了 BMP、磷酸化(p)-母亲抗Decapentaplegic 同源物-1(Smad1)和 p-丝裂原活化蛋白激酶(p38MAPK)的蛋白表达水平。这些结果表明,机械应力通过 BMP-Smad1 和 Src-p38MAPK 信号通路有效增加细胞增殖,促进 OLF 细胞的成骨分化率,激活 OC、ALP 和 RUNX-2,并抑制 Ets-1 和 SOX-2。