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学科主题: 口腔医学
题名:
Heterodimeric BMP-2/7 Antagonizes the Inhibition of All-Trans Retinoic Acid and Promotes the Osteoblastogenesis
作者: Bi, Wenjuan1; Gu, Zhiyuan1,2; Zheng, Yuanna2; Zhang, Xiao3; Guo, Jing4,5; Wu, Gang5,6
刊名: PLOS ONE
发表日期: 2013-10-30
DOI: 10.1371/journal.pone.0078198
卷: 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
所属项目编号: Y2111175 ; 17110008
项目资助者: Natural Science Foundation of Zhejiang Province ; Research Foundation of Zhejiang Chinese Medical University
WOS记录号: WOS:000326334500101
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55344
Appears in Collections:北京大学口腔医学院_口腔修复科_期刊论文

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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

Recommended Citation:
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).
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