RETRACTED: P38 and ERK1/2 MAPKs Act in Opposition to Regulate BMP9-Induced Osteogenic Differentiation of Mesenchymal Progenitor Cells (Retracted Article)

被引:52
作者
Zhao, Yingze [1 ]
Song, Tao [1 ]
Wang, Wenjuan [1 ]
Wang, Jin [1 ]
He, Juanwen [1 ]
Wu, Ningning [1 ]
Tang, Min [1 ]
He, Baicheng [1 ]
Luo, Jinyong [1 ]
机构
[1] Chongqing Med Univ, Chinese Minist Educ, Key Lab Diagnost Med, Chongqing, Peoples R China
关键词
BONE MORPHOGENETIC PROTEINS; MARROW STROMAL CELLS; STEM-CELLS; OSTEOBLAST DIFFERENTIATION; GENE-THERAPY; BMP-2; GENE; TRANSCRIPTION FACTOR; SKELETAL DEVELOPMENT; SIGNALING PATHWAYS; OSTEOCALCIN GENE;
D O I
10.1371/journal.pone.0043383
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Although previous studies have demonstrated that BMP9 is highly capable of inducing osteogenic differentiation and bone formation, the precise molecular mechanism involved remains to be fully elucidated. In this current study, we explore the possible involvement and detail effects of p38 and ERK1/2 MAPKs on BMP9-indcued osteogenic differentiation of mesenchymal progenitor cell (MPCs). We find that BMP9 simultaneously stimulates the activation of p38 and ERK1/2 in MPCs. BMP9-induced early osteogenic marker, such as alkaline phosphatase (ALP), and late osteogenic markers, such as matrix mineralization and osteocalcin (OC) are inhibited by p38 inhibitor SB203580, whereas enhanced by ERK1/2 inhibitor PD98059. BMP9-induced activation of Runx2 and Smads signaling are reduced by SB203580, and yet increased by PD98059 in MPCs. The in vitro effects of inhibitors are reproduced with adenoviruses expressing siRNA targeted p38 and ERK1/2, respectively. Using mouse calvarial organ culture and subcutaneous MPCs implantation, we find that inhibition of p38 activity leads to significant decrease in BMP9-induced osteogenic differentiation and bone formation, however, blockage of ERK1/2 results in effective increase in BMP9-indcued osteogenic differentiation in vivo. Together, our results reveal that p38 and ERK1/2 MAPKs are activated in BMP9-induced osteogenic differentiation of MPCs. What is most noteworthy, however, is that p38 and ERK1/2 act in opposition to regulate BMP9-induced osteogenic differentiation of MPCs.
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页数:13
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