An osteopontin-integrin interaction plays a critical role in directing adipogenesis and osteogenesis by mesenchymal stem cells.
An osteopontin-integrin interaction plays a critical role in directing adipogenesis and osteogenesis by mesenchymal stem cells.
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DOI：
10.1002/stem.1567
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发表时间：
2014-02
期刊：
影响因子：
5.2
通讯作者：
Shi, Yufang
中科院分区：
文献类型：
--
作者：
Chen, Qing;Shou, Peishun;Zhang, Liying;Xu, Chunliang;Zheng, Chunxing;Han, Yanyan;Li, Wenzhao;Huang, Yin;Zhang, Xiaoren;Shao, Changshun;Roberts, Arthur I.;Rabson, Arnold B.;Ren, Guangwen;Zhang, Yanyun;Wang, Ying;Denhardt, David T.;Shi, Yufang
An imbalance between normal adipogenesis and osteogenesis by mesenchymal stem cells (MSCs) has been shown to be related to various human metabolic diseases, such as obesity and osteoporosis; however, the underlying mechanisms remain elusive. We found that the interaction between osteopontin (OPN), an arginine-glycine-aspartate-containing glycoprotein, and integrin αv/β1 plays a critical role in the lineage determination of MSCs. Although OPN is a well established marker during osteogenesis, its role in MSC differentiation is still unknown. Our study reveals that blockade of OPN function promoted robust adipogenic differentiation, while inhibiting osteogenic differentiation. Re-expression of OPN restored a normal balance between adipogenesis and osteogenesis in OPN-/- MSCs. Retarded bone formation by OPN-/- MSCs was also verified by in vivo implantation with hydroxyapatite-tricalcium phosphate (HA-TCP), a bone-forming matrix. The role of extracellular OPN in MSC differentiation was further demonstrated by supplementation and neutralization of OPN. Blocking well-known OPN receptors integrin αv/β1 but not CD44, also affected MSC differentiation. Further studies revealed that OPN inhibits the C/EBPs signaling pathway through integrin αv/β1. Consistent with these in vitro results, OPN-/- mice had a higher fat to total body weight ratio than did wild-type mice. Therefore, our study demonstrates a novel role for OPN-integrin αv/β1 in regulating MSC differentiation.
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影响因子：
3.7
作者：
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DOI：
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发表时间：
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