中国科学院深圳先进技术研究院机构知识库(SIAT OpenIR): LIM domain proteins Pinch1/2 regulate chondrogenesis and bone mass in mice
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LIM domain proteins Pinch1/2 regulate chondrogenesis and bone mass in mice
Lei, Yiming; Fu, Xuekun; Li, Pengyu; Lin, Sixiong; Yan, Qinnan; Lai, Yumei; Liu, Xin; Wang, Yishu; Bai, Xiaochun; Liu, Chuanju; Chen, Di; Zou, Xuenong; Cao, Xu; Cao, Huiling; Xiao, Guozhi
2020
Source PublicationBONE RESEARCH
Subtype期刊论文
AbstractThe LIM domain-containing proteins Pinch1/2 regulate integrin activation and cell-extracellular matrix interaction and adhesion. Here, we report that deleting Pinch1 in limb mesenchymal stem cells (MSCs) and Pinch2 globally (double knockout; dKO) in mice causes severe chondrodysplasia, while single mutant mice do not display marked defects. Pinch deletion decreases chondrocyte proliferation, accelerates cell differentiation and disrupts column formation. Pinch loss drastically reduces Smad2/3 protein expression in proliferative zone (PZ) chondrocytes and increases Runx2 and Col10a1 expression in both PZ and hypertrophic zone (HZ) chondrocytes. Pinch loss increases sclerostin and Rankl expression in HZ chondrocytes, reduces bone formation, and increases bone resorption, leading to low bone mass. In vitro studies revealed that Pinch1 and Smad2/3 colocalize in the nuclei of chondrocytes. Through its C-terminal region, Pinch1 interacts with Smad2/3 proteins. Pinch loss increases Smad2/3 ubiquitination and degradation in primary bone marrow stromal cells (BMSCs). Pinch loss reduces TGF-beta-induced Smad2/3 phosphorylation and nuclear localization in primary BMSCs. Interestingly, compared to those from single mutant mice, BMSCs from dKO mice express dramatically lower protein levels of beta-catenin and Yap1/Taz and display reduced osteogenic but increased adipogenic differentiation capacity. Finally, ablating Pinch1 in chondrocytes and Pinch2 globally causes severe osteopenia with subtle limb shortening. Collectively, our findings demonstrate critical roles for Pinch1/2 and a functional redundancy of both factors in the control of chondrogenesis and bone mass through distinct mechanisms.
Indexed BySCI
Language英语
EI Accession Number退行性
Document Type期刊论文
Identifierhttp://ir.siat.ac.cn/handle/172644/18294
Collection医药所
Recommended Citation
GB/T 7714
Lei, Yiming,Fu, Xuekun,Li, Pengyu,et al. LIM domain proteins Pinch1/2 regulate chondrogenesis and bone mass in mice[J]. BONE RESEARCH,2020.
APA Lei, Yiming.,Fu, Xuekun.,Li, Pengyu.,Lin, Sixiong.,Yan, Qinnan.,...&Xiao, Guozhi.(2020).LIM domain proteins Pinch1/2 regulate chondrogenesis and bone mass in mice.BONE RESEARCH.
MLA Lei, Yiming,et al."LIM domain proteins Pinch1/2 regulate chondrogenesis and bone mass in mice".BONE RESEARCH (2020).
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