A Comprehensive Analysis of the Dual Roles of BMPs in Regulating Adipogenic and Osteogenic Differentiation of Mesenchymal Progenitor Cells

被引：337

作者：

Kang, Quan ^{[1
,2
,3
]}

Song, Wen-Xin ^{[1
,2
,3
]}

Luo, Qing ^{[1
,2
,3
]}

Tang, Ni ^{[1
,2
,3
,4
]}

Luo, Jinyong ^{[1
,2
,3
]}

Luo, Xiaoji ^{[1
,2
,3
]}

Chen, Jin ^{[1
,2
,3
]}

Bi, Yang ^{[1
,2
,3
]}

He, Bai-Cheng ^{[1
,2
,3
]}

Park, Jong Kyung ^{[2
,3
,5
]}

Jiang, Wei ^{[1
]}

Tang, Yi ^{[6
]}

Huang, Jiayi ^{[1
,2
,3
]}

Su, Yuxi ^{[1
,2
,3
]}

Zhu, Gao-Hui ^{[1
,2
,3
]}

He, Yun ^{[1
,2
,3
]}

Yin, Hong ^{[1
]}

Hu, Zhenming ^{[2
,3
]}

Wang, Yi ^{[1
,2
,3
]}

Chen, Liang ^{[1
,2
,3
,4
]}

Zuo, Guo-Wei ^{[1
,2
,3
]}

Pan, Xiaochuan ^{[7
]}

Shen, Jikun ^{[1
]}

Vokes, Tamara ^{[8
]}

Reid, Russell R. ^{[1
]}

Haydon, Rex C. ^{[1
]}

Luu, Hue H. ^{[1
]}

He, Tong-Chuan ^{[1
,2
,3
]}

机构：

[1] Univ Chicago, Med Ctr, Mol Oncol Lab, Dept Surg, Chicago, IL 60637 USA

[2] Chinese Minist Educ, Key Lab Diagnost Med, Chongqing, Peoples R China

[3] Chongqing Med Univ, Childrens Hosp, Chongqing, Peoples R China

[4] Chongqing Med Univ, Affiliated Hosp 2, Chongqing, Peoples R China

[5] Catholic Univ Korea, St Pauls Hosp, Coll Med, Dept Surg, Seoul, South Korea

[6] Northwestern Univ, Childrens Mem Hosp, Dept Pathol, Chicago, IL 60614 USA

[7] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA

[8] Univ Chicago, Endocrinol Sect, Chicago, IL 60637 USA

来源：

STEM CELLS AND DEVELOPMENT | 2009年 / 18卷 / 04期

基金：

美国国家卫生研究院;

关键词：

BONE MORPHOGENETIC PROTEINS; STEM-CELLS; OSTEOBLAST DIFFERENTIATION; ADIPOCYTE DIFFERENTIATION; MULTILINEAGE DIFFERENTIATION; C3H10T1/2; CELLS; MARROW; WNT; TISSUE; EXPRESSION;

D O I：

10.1089/scd.2008.0130

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Pluripotent mesenchymal stem cells (MSCs) are bone marrow stromal progenitor cells that can differentiate into osteogenic, chondrogenic, adipogenic, and myogenic lineages. Several signaling pathways have been shown to regulate the lineage commitment and terminal differentiation of MSCs. Here, we conducted a comprehensive analysis of the 14 types of bone morphogenetic protein (BMPs) for their abilities to regulate multilineage specific differentiation of MSCs. We found that most BMPs exhibited distinct abilities to regulate the expression of Runx2, Sox9, MyoD, and PPAR gamma 2. Further analysis indicated that BMP-2, BMP-4, BMP-6, BMP-7, and BMP-9 effectively induced both adipogenic and osteogenic differentiation in vitro and in vivo. BMP-induced commitment to osteogenic or adipogenic lineage was shown to be mutually exclusive. Overexpression of Runx2 enhanced BMP-induced osteogenic differentiation, whereas knockdown of Runx2 expression diminished BMP-induced bone formation with a decrease in adipocyte accumulation in vivo. Interestingly, overexpression of PPAR gamma 2 not only promoted adipogenic differentiation, but also enhanced osteogenic differentiation upon BMP-2, BMP-6, and BMP-9 stimulation. Conversely, MSCs with PPAR gamma 2 knockdown or mouse embryonic fibroblasts derived from PPAR gamma 2(-/-) mice exhibited a marked decrease in adipogenic differentiation, coupled with reduced osteogenic differentiation and diminished mineralization upon BMP-9 stimulation, suggesting that PPAR gamma 2 may play a role in BMP-induced osteogenic and adipogenic differentiation. Thus, it is important to understand the molecular mechanism behind BMP-regulated lineage divergence during MSC differentiation, as this knowledge could help us to understand the pathogenesis of skeletal diseases and may lead to the development of strategies for regenerative medicine.

引用

页码：545 / U33

页数：15

共 72 条

[1] EXPRESSION OF HUMAN BONE MORPHOGENETIC PROTEINS-2 OR PROTEINS-4 IN MURINE MESENCHYMAL PROGENITOR C3H10T1/2 CELLS INDUCES DIFFERENTIATION INTO DISTINCT MESENCHYMAL CELL LINEAGES [J].