Downregulation of GNAS inhibits osteogenesis of bone marrow mesenchymal stem cells and promotes osteoporosis through the Wnt pathway

X. Zheng, Y.-C. Wang, N. Zhu, D.-Y. Cai, X.-K. Gong, S. Mei, W.-J. Chen, T. Chen, J.-W. Ruan

Department of Orthopedics, Taizhou Municipal Hospital, Taizhou, Zhejiang Province, China. chentaotz@163.com

 

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• Stem Cells

OBJECTIVE: This study aims to explore the role of GNAS in accelerating the progression of osteoporosis by inhibiting osteogenesis of BMSCs by the Wnt pathway.

PATIENTS AND METHODS: GNAS levels in OP tissues and BMSCs undergoing osteogenesis for different time points were detected. Regulatory effects of GNAS on osteogenesis-related gene expressions, ALP activity, capability of mineralization, and activation of the Wnt pathway in BMSCs were assessed through a series of functional experiments. At last, rescue experiments were performed to further verify the significance of the Wnt pathway during GNAS-mediated osteogenesis development.

RESULTS: GNAS was downregulated in OP tissues relative to normal bone tissues. With the prolongation of osteogenesis, GNAS level gradually increased in BMSCs. Knockdown of GNAS downregulated expression levels of ALP and RUNX2, and attenuated ALP activity and capability of mineralization in BMSCs. GNAS was able to activate the Wnt pathway in BMSCs. Notably, overexpression of Wnt3a could reverse the regulatory effects of GNAS on osteogenesis-related gene expressions, ALP activity, and capability of mineralization in BMSCs.

CONCLUSIONS: Downregulation of GNAS suppresses osteogenesis of BMSCs through the Wnt pathway, thus aggravating the progression of osteoporosis.

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