Fu Hong-Dan, Wang Hai-Rui, Li Dai-He
Immunization Section, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010010, P.R. China.
Department of Orthopedics, The Affiliated People's Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010010, P.R. China.
Exp Ther Med. 2017 Dec;14(6):5424-5428. doi: 10.3892/etm.2017.5210. Epub 2017 Sep 27.
Mesenchymal stem cells (MSCs) are able to differentiate into adipocytes, chondroblasts or cartilage under different stimulation conditions. Identifying a mechanism that triggers the differentiation of MSCs into cartilage may help the development of novel therapeutic approaches for heterotopic ossification, the pathological formation of lamellar bone in soft tissue outside the skeleton that may lead to debilitating immobility. Bone morphogenetic proteins (BMPs), including BMP-7, are the most potent growth factors for enhancing bone formation. The current study aimed to understand the potential involvement of the Wnt/β-catenin signaling pathway in the BMP-7-induced growth of rabbit MSCs (rMSCs). Different concentrations of BMP-7 were applied to cultured rMSCs, and proliferation was evaluated by MTT assay. Changes in the phosphorylation state of glycogen synthase kinase (GSK)-3β, in addition to the expression levels of alkaline phosphatase, β-catenin and runt-related transcription factor 2 were observed by western blot analysis. Following treatment with BMP-7, the phosphorylation of GSK-3β was stimulated and the expression of β-catenin, ALP and Runx2 was increased. Furthermore, inhibiting β-catenin signaling with XAV-939 suppressed the BMP-7-mediated changes. The results indicated that the BMP-7-induced differentiation of rMSCs into cartilage was promoted primarily by the Wnt/β-catenin pathway.
间充质干细胞（MSCs）在不同的刺激条件下能够分化为脂肪细胞、成软骨细胞或软骨。确定一种触发MSCs向软骨分化的机制可能有助于开发针对异位骨化的新型治疗方法，异位骨化是指在骨骼外软组织中病理性形成板层骨，可能导致使人衰弱的活动障碍。骨形态发生蛋白（BMPs），包括BMP - 7，是增强骨形成的最有效的生长因子。当前的研究旨在了解Wnt/β-连环蛋白信号通路在BMP - 7诱导的兔间充质干细胞（rMSCs）生长中的潜在作用。将不同浓度的BMP - 7应用于培养的rMSCs，并通过MTT法评估细胞增殖。通过蛋白质免疫印迹分析观察糖原合酶激酶（GSK）-3β的磷酸化状态变化，以及碱性磷酸酶、β-连环蛋白和 runt相关转录因子2的表达水平变化。用BMP - 7处理后，GSK - 3β的磷酸化受到刺激，β-连环蛋白、碱性磷酸酶（ALP）和Runx2的表达增加。此外，用XAV - 939抑制β-连环蛋白信号传导可抑制BMP - 7介导的变化。结果表明，BMP - 7诱导的rMSCs向软骨的分化主要由Wnt/β-连环蛋白途径促进。
