An Osteopontin-Integrin Interaction Plays a Critical Role in Directing Adipogenesis and Osteogenesis by Mesenchymal Stem Cells. (13th January 2014)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Stem cells. Volume 32:Number 2(2014:Feb.)
• Page Start: 327
• Page End: 337
• Publication Date: 2014-01-13
• Subjects: Adipocytes -- Osteoblasts -- Integrins -- C/EBP -- Differentiation; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1567
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract : 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, 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. Stem Cells 2014;32:327–337