Improving the osteogenic efficacy of BMP2 with mechano growth factor by regulating the signaling events in BMP pathway

被引:12
|
作者
Deng, Moyuan [1 ,2 ]
Liu, Peng [3 ,4 ]
Xiao, Hualiang [5 ]
Zhang, Yuanyuan [6 ]
Wang, Yuanliang [1 ]
Zhao, Jianhua [3 ,4 ]
Xu, Jianzhong [2 ]
机构
[1] Chongqing Univ, Bioengn Coll, Res Ctr Bioinspired Mat Sci & Engn, Chongqing 400030, Peoples R China
[2] Third Mil Med Univ, Southwest Hosp, Dept Orthopaed, Natl & Reg United Engn Lab Tissue Engn, Chongqing, Peoples R China
[3] Daping Hosp, Dept Orthopaed, Chongqing 400042, Peoples R China
[4] Inst Surg Res, Chongqing 400042, Peoples R China
[5] Third Mil Med Univ, Daping Hosp, Dept Pathol, Chongqing 400042, Peoples R China
[6] Wake Forest Univ, Bowman Gray Sch Med, Wake Forest Inst Regenerat Med, Winston Salem, NC 27157 USA
关键词
BMP2; MGF24E; BMP/Smad pathway; Osteogenesis; Bone defect healing; MESENCHYMAL STEM-CELLS; FACTOR DELIVERY; BONE-FORMATION; EXPRESSION; OSTEOBLASTS; PEPTIDE; DIFFERENTIATION; ACTIVATION; PROTEINS; OVERLOAD;
D O I
10.1007/s00441-015-2154-3
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Local application of bone morphogenetic protein 2 (BMP2) is known to promote large bone defect healing and BMP2-initiated bone regeneration could be enhanced by an additional mechanical stimulation. The C-terminal 24-a.a. peptide of mechano growth factor (MGF24E), a mechanical-sensitive molecule, has been demonstrated to promote bone healing. Here, we propose a hypothesis that MGF24E could also improve the osteogenic efficacy of BMP2 by regulating the signaling events in the BMP pathway. To confirm the hypothesis, the potentials of MGF24E, BMP2 and BMP2/MGF24E combination treatments on the phosphorylation of Smad 1/5/8, the downstream osteogenesis-related gene expression and osteoblasts mineralization, are investigated with or without the blocking of Smad 5 siRNA. Furthermore, 15-mm rabbit radial bone defects were healed with the cytokine treatments and then evaluated by radiographic examination, histological assessment and immunohistochemical analysis. MGF24E could enhance the BMP2-induced Smad signaling pathway by upregulating the p-Smad protein expression and the downstream osteogenic gene expression. An amount of 5 nM BMP2 in a sub-25 nM concentration of MGF24E medium achieved a higher expression for ALP mRNA and a greater calcium mineral content compared with BMP2 alone. Nevertheless, the inhibition of the MGF24E-regulated BMP pathway could block osteogenesis induced by the dual treatment. In vivo, MGF24E treatment upregulated the endogenous BMP2 expression and the addition of MGF24E into the BMP2 treatment remarkably enhanced the bone mineral density (BMD), the radiographic scores and the histological restoration of the regenerated tissue against BMP2 treatment, suggesting a new strategy for BMP2 in bone defect healing.
引用
收藏
页码:723 / 731
页数:9
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