The role of COX-2 in mediating the effect of PTEN on BMP9 induced osteogenic differentiation in mouse embryonic fibroblasts

被引：42

作者：

Huang, Jun ^{[1
,2
]}

Yuan, Shuang-Xue ^{[1
,2
]}

Wang, Dong-Xu ^{[1
,2
]}

Wu, Qiu-Xiang ^{[1
,2
]}

Wang, Xing ^{[2
,3
]}

Pi, Chang-Jun ^{[2
,3
]}

Zou, Xiang ^{[2
,3
]}

Chen, Liang ^{[2
,3
]}

Ying, Liang-Jun ^{[2
,3
]}

Wu, Ke ^{[1
,2
]}

Yang, Jun-Qing ^{[1
,2
]}

Sun, Wen-Juan ^{[1
,2
]}

Deng, Zhong-Liang ^{[2
,3
]}

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

机构：

[1] Chongqing Med Univ, Dept Pharmacol, Sch Pharm, Chongqing 400016, Peoples R China

[2] Key Lab Biochem & Mol Pharmacol Chongqing, Chongqing, Peoples R China

[3] Chongqing Med Univ, Affiliated Hosp 2, Dept Orthoped Surg, Chongqing 400016, Peoples R China

来源：

BIOMATERIALS | 2014年 / 35卷 / 36期

关键词：

BMP9; PTEN; Osteogenic differentiation; MEFs; PI3K/Akt; COX-2; MESENCHYMAL STEM-CELLS; SIGNAL-TRANSDUCTION; BONE-FORMATION; CYCLOOXYGENASE-2; INSIGHTS; PATHWAY; GROWTH; PLAYS; LOOP;

D O I：

10.1016/j.biomaterials.2014.08.016

中图分类号：

R318 [生物医学工程];

学科分类号：

100103 [病原生物学];

摘要：

Mouse embryonic fibroblasts (MEFs) are multi-potent progenitor cells (MPCs), can differentiate into different lineages, such as osteogenic, and adipogenic. PTEN, a tumor suppressor, may be involved in regulating bone development through interacting with COX-2. BMP9, the most potent osteogenic BMPs, can up-regulate COX-2 in MPCs. Whether PTEN is involved in BMP9 induced osteogenic differentiation in MPCs remains unknown. The goal of this investigation is to identify the effect of PTEN on BMP9-induced osteogenic differentiation in MPCs and dissect the possible mechanism underlay this. We found that BMP9 down-regulates PTEN, and PTEN inhibitor (VO) effectively increases different osteogenic markers induced by BMP9 in MEFs. Exogenous expression of PTEN inhibits BMP9 induced ectopic bone formation apparently. Mechanistically, we found that VO can enhance BMP9 induced BMPs/Smads signaling prominently without no substantial effects on cell cycle. Further analysis indicates that VO can promote BMP9-induced expression of COX-2 in MEFs, which can be eliminated by PI3K inhibitor. Additionally, COX-2 knockdown abolishes the effect of VO on BMP9-induced ALP activities in MEFs. Our findings suggest that PTEN plays an important role in regulating BMP9 induced osteogenic differentiation in MPCs, which may be mediated by PTEN/PI3K/Akt signaling to modulate the expression of COX-2. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：9649 / 9659

页数：11

共 49 条

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