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

被引:0
|
作者
Moyuan Deng
Peng Liu
Hualiang Xiao
Yuanyuan Zhang
Yuanliang Wang
Jianhua Zhao
Jianzhong Xu
机构
[1] Chongqing University,Research Center of Bioinspired Materials Science and Engineering, Bioengineering College
[2] Southwest Hospital of Third Military Medical University,National & Regional United Engineering Lab of Tissue Engineering, Department of Orthopaedic
[3] Daping Hospital and Research Institute of Surgery,Department of Orthopaedics
[4] Third Military Medical University,Department of Pathology, Daping Hospital
[5] Wake Forest University School of Medicine,Wake Forest Institute for Regenerative Medicine
来源
Cell and Tissue Research | 2015年 / 361卷
关键词
BMP2; MGF24E; BMP/Smad pathway; Osteogenesis; Bone defect healing;
D O I
暂无
中图分类号
学科分类号
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.
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页码:723 / 731
页数:8
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