Wnt信号通路
间充质干细胞
骨质疏松症
下调和上调
细胞生物学
生物
骨髓
癌症研究
人口
信号转导
内分泌学
免疫学
医学
基因
遗传学
环境卫生
作者
Dongdong Fei,Yang Zhang,Junjie Wu,Hui Zhang,Anqi Liu,Xiaoning He,Jinjin Wang,Bei Li,Qintao Wang,Yan Jin
出处
期刊:Aging Cell
[Wiley]
日期:2019-05-23
卷期号:18 (4)
被引量:23
摘要
Aims Age-related bone mass loss is one of the most prevalent diseases that afflict the elderly population. The decline in the osteogenic differentiation capacity of bone marrow-derived mesenchymal stem cells (BMMSCs) is regarded as one of the central mediators. Voltage-gated Ca2+ channels (VGCCs) play an important role in the regulation of various cell biological functions, and disruption of VGCCs is associated with several age-related cellular characteristics and systemic symptoms. However, whether and how VGCCs cause the decreased osteogenic differentiation abilities of BMMSCs have not been fully elucidated. Methods Voltage-gated Ca2+ channels related genes were screened, and the candidate gene was determined in several aging models. Functional role of determined channel on osteogenic differentiation of BMMSCs was investigated through gain and loss of function experiments. Molecular mechanism was explored, and intervention experiments in vivo and in vitro were performed. Results We found that Cav1.2 was downregulated in these aging models, and downregulation of Cav1.2 in Zmpste24−/− BMMSCs contributed to compromised osteogenic capacity. Mechanistically, Cav1.2 regulated the osteogenesis of BMMSCs through canonical Wnt/β-catenin pathway. Moreover, upregulating the activity of Cav1.2 mitigated osteoporosis symptom in Zmpste24−/− mice. Conclusion Impaired osteogenic differentiation of Zmpste24−/− BMMSCs can be partly attributed to the decreased Cav1.2 expression, which leads to the inhibition of canonical Wnt pathway. Bay K8644 treatment could be an applicable approach for treating age-related bone loss by ameliorating compromised osteogenic differentiation capacity through targeting Cav1.2 channel.
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