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骨形态发生蛋白 2 通过 Wnt/β-连环蛋白信号通路促进软骨细胞增殖。

BMP2 promotes chondrocyte proliferation via the Wnt/β-catenin signaling pathway.

机构信息

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Minhou Shangjie, Fuzhou, People's Republic of China.

出版信息

Mol Med Rep. 2011 Jul-Aug;4(4):621-6. doi: 10.3892/mmr.2011.474. Epub 2011 Apr 14.

Abstract

Bone morphogenetic protein 2 (BMP2), a member of the transforming growth factor-β (TGF-β) superfamily, plays a key role in the induction of the differentiation of mesenchymal cells into chondrocytes to form cartilage tissue. However, it is not clear whether BMP2 regulates the proliferation of chondrocytes. In the present study, the effect of BMP2 on the proliferation of chondrocytes and its underlying mechanism was investigated. Chondrocytes isolated from the knee of SD rats were cultured and identified using toluidine blue staining. The second generation chondrocytes were collected and stimulated with or without BMP2 for 48 h. Cell viability was analyzed using the MTT assay. mRNA and protein expression levels of β-catenin, GSK-3β, Dvl1 and Cyclin D1 were detected using real-time RT-PCR and Western blotting, respectively. The cell cycle distribution of the chondrocytes was analyzed by flow cytometry. BMP2 stimulation was found to significantly increase cell viability. In addition, following BMP2 treatment, β-catenin, Cyclin D1 and Dvl1 expression was significantly increased, whereas GSK-3β expression was significantly decreased. Moreover, the percentage proportion of chondrocytes in the G0/G1 phase was significantly decreased, whereas that in the S phase was significantly increased. The results indicate that BMP2 promotes chondrocyte proliferation via the Wnt/β-catenin signaling pathway.

摘要

骨形态发生蛋白 2(BMP2)是转化生长因子-β(TGF-β)超家族的成员,在诱导间充质细胞分化为软骨细胞形成软骨组织中发挥关键作用。然而,BMP2 是否调节软骨细胞的增殖尚不清楚。本研究探讨了 BMP2 对软骨细胞增殖的影响及其潜在机制。采用甲苯胺蓝染色法培养和鉴定来自 SD 大鼠膝关节的软骨细胞。收集第二代软骨细胞,并用或不用 BMP2 刺激 48 h。采用 MTT 法分析细胞活力。采用实时 RT-PCR 和 Western blot 分别检测β-catenin、GSK-3β、Dvl1 和 Cyclin D1 的 mRNA 和蛋白表达水平。采用流式细胞术分析软骨细胞的细胞周期分布。BMP2 刺激显著增加细胞活力。此外,BMP2 处理后β-catenin、Cyclin D1 和 Dvl1 的表达显著增加,而 GSK-3β 的表达显著降低。此外,G0/G1 期的软骨细胞比例显著降低,而 S 期的软骨细胞比例显著增加。这些结果表明,BMP2 通过 Wnt/β-catenin 信号通路促进软骨细胞增殖。

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