An Osteopontin-Integrin Interaction Plays a Critical Role in Directing Adipogenesis and Osteogenesis by Mesenchymal Stem Cells

被引：291

作者：

Chen, Qing ^{[1
]}

Shou, Peishun ^{[1
]}

Zhang, Liying ^{[2
]}

Xu, Chunliang ^{[1
]}

Zheng, Chunxing ^{[1
]}

Han, Yanyan ^{[1
]}

Li, Wenzhao ^{[1
]}

Huang, Yin ^{[1
]}

Zhang, Xiaoren ^{[1
]}

Shao, Changshun ^{[3
]}

Roberts, Arthur I. ^{[2
]}

Rabson, Arnold B. ^{[2
]}

Ren, Guangwen ^{[2
]}

Zhang, Yanyun ^{[1
]}

Wang, Ying ^{[1
]}

Denhardt, David T. ^{[4
]}

Shi, Yufang ^{[1
,2
]}

机构：

[1] Shanghai Jiao Tong Univ, Shanghai Inst Biol Sci, Chinese Acad Sci, Key Lab Stem Cell Biol,Inst Hlth Sci,Sch Med, Shanghai 200030, Peoples R China

[2] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Child Hlth Inst New Jersey, New Brunswick, NJ USA

[3] Rutgers State Univ, Dept Genet, Piscataway, NJ USA

[4] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ USA

来源：

STEM CELLS | 2014年 / 32卷 / 02期

基金：

美国国家卫生研究院;

关键词：

Adipocytes; Osteoblasts; Integrins; C; EBP; Differentiation; BONE-MARROW; ADIPOCYTE DIFFERENTIATION; OSTEOBLAST DIFFERENTIATION; INTRACELLULAR OSTEOPONTIN; MEDIATED IMMUNOSUPPRESSION; MICE LACKING; WEIGHT-LOSS; NICHE; OSTEOPOROSIS; COMPONENT;

D O I：

10.1002/stem.1567

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

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 v/1 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 v/1 but not CD44 also affected MSC differentiation. Further studies revealed that OPN inhibits the C/EBPs signaling pathway through integrin v/1. 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 v/1 in regulating MSC differentiation. Stem Cells2014;32:327-337

引用

页码：327 / 337

页数：11

共 57 条

[1]

Osteoblastic cells regulate the haematopoietic stem cell niche [J].