An osteopontin-integrin interaction plays a critical role in directing adipogenesis and osteogenesis by mesenchymal stem cells

Qing Chen, Peishun Shou, Liying Zhang, Chunliang Xu, Chunxing Zheng, Yanyan Han, Wenzhao Li, Yin Huang, Xiaoren Zhang, Changshun Shao, Arthur I. Roberts, Arnold B. Rabson, Guangwen Ren, Yanyun Zhang, Ying Wang, David T. Denhardt, Yufang Shi

Research output: Contribution to journalArticle

110 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)327-337
Number of pages11
JournalSTEM CELLS
Volume32
Issue number2
DOIs
StatePublished - Feb 1 2014

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Keywords

  • Adipocytes
  • C/EBP
  • Differentiation
  • Integrins
  • Osteoblasts

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Chen, Q., Shou, P., Zhang, L., Xu, C., Zheng, C., Han, Y., Li, W., Huang, Y., Zhang, X., Shao, C., Roberts, A. I., Rabson, A. B., Ren, G., Zhang, Y., Wang, Y., Denhardt, D. T., & Shi, Y. (2014). An osteopontin-integrin interaction plays a critical role in directing adipogenesis and osteogenesis by mesenchymal stem cells. STEM CELLS, 32(2), 327-337. https://doi.org/10.1002/stem.1567