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学科主题口腔医学
Heterodimeric BMP-2/7 Antagonizes the Inhibition of All-Trans Retinoic Acid and Promotes the Osteoblastogenesis
Bi, Wenjuan1; Gu, Zhiyuan1,2; Zheng, Yuanna2; Zhang, Xiao3; Guo, Jing4,5; Wu, Gang5,6
刊名PLOS ONE
2013-10-30
DOI10.1371/journal.pone.0078198
8期:10
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]OSTEOCLASTIC BONE-RESORPTION ; OSTEOGENIC DIFFERENTIATION ; HYDROXYAPATITE IMPLANTS ; RHBMP2/7 HETERODIMER ; GENE-EXPRESSION ; RECEPTOR-GAMMA ; SMAD PROTEINS ; CELL-CYCLE ; RAT MODEL ; PATHWAYS
英文摘要

Objectives: Hypervitaminosis A and alcoholism can result in a low mineral density and compromised regenerative capacity of bone, thus delaying implant osteointegration. The inhibitory effect of all-trans retinoic acid on osteoblastogenesis is considered to be one of the mechanisms. We hypothesized that heterodimeric bone morphogenetic protein-2/7 could antagonize all-trans retinoic acid and enhance osteoblastogenesis, with an aim to accelerate and enhance bone regeneration and implant osteointegration.

Materials and Methods: We applied 5 ng/ml or 50 ng/ml bone morphogenetic protein-2/7 to restore the osteoblastogenesis of pre-osteoblasts (MC3T3-E1 cell line) that was inhibited by 1 mu M all-trans retinoic acid. We evaluated the efficacy by assessing cell numbers (proliferation), alkaline phosphatase activity (a marker for early differentiation), osteocalcin (a marker for late differentiation), calcium deposition (a marker for final mineralization) and the expression of osteoblastogenic genes (such as Runx2, Collagen Ia, alkaline phosphatase and osteocalcin) at different time points.

Results: All-trans retinoic acid significantly inhibited the expression of all the tested osteoblastogenic genes and proteins except alkaline phosphatase activity. In the presence of ATRA, 50 ng/ml bone morphogenetic protein-2/7 not only completely restored but also significantly enhanced all the osteoblastogenic genes and proteins. On the 28th day, mineralization was completely inhibited by all-trans retinoic acid. In contrast, 50 ng/ml BMP-2/7 could antagonize ATRA and significantly enhance the mineralization about 2.5 folds in comparison with the control treatment (no ATRA, no BMP2/7).

Conclusions: Heterodimeric bone morphogenetic protein-2/7 bears a promising application potential to significantly promote bone regeneration and implant osteointegration for the patients with hypervitaminosis A and alcoholism.

语种英语
WOS记录号WOS:000326334500101
项目编号Y2111175 ; 17110008
资助机构Natural Science Foundation of Zhejiang Province ; Research Foundation of Zhejiang Chinese Medical University
引用统计
被引频次:7[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/55344
专题北京大学口腔医学院_口腔修复科
作者单位1.Univ Amsterdam, Amsterdam, Netherlands
2.Zhejiang Univ, Sch Hosp Stomatol, Hangzhou 310003, Zhejiang, Peoples R China
3.Zhejiang Chinese Med Univ, Sch Stomatol, Hangzhou, Zhejiang, Peoples R China
4.Peking Univ, Dept Prosthodont, Sch & Hosp Stomatol, Beijing 100871, Peoples R China
5.Vrije Univ Amsterdam, Res Inst MOVE, Dept Oral Cell Biol, Acad Ctr Dent Amsterdam ACTA, Amsterdam, Netherlands
6.Vrije Univ Amsterdam, Res Inst MOVE, Acad Ctr Dent Amsterdam ACTA, Dept Oral Implantol & Prosthet Dent, Amsterdam, Netherlands
推荐引用方式
GB/T 7714
Bi, Wenjuan,Gu, Zhiyuan,Zheng, Yuanna,et al. Heterodimeric BMP-2/7 Antagonizes the Inhibition of All-Trans Retinoic Acid and Promotes the Osteoblastogenesis[J]. PLOS ONE,2013,8(10).
APA Bi, Wenjuan,Gu, Zhiyuan,Zheng, Yuanna,Zhang, Xiao,Guo, Jing,&Wu, Gang.(2013).Heterodimeric BMP-2/7 Antagonizes the Inhibition of All-Trans Retinoic Acid and Promotes the Osteoblastogenesis.PLOS ONE,8(10).
MLA Bi, Wenjuan,et al."Heterodimeric BMP-2/7 Antagonizes the Inhibition of All-Trans Retinoic Acid and Promotes the Osteoblastogenesis".PLOS ONE 8.10(2013).
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