All-trans retinoic-acid inhibits heterodimeric bone morphogenetic protein 2/7-stimulated osteoclastogenesis, and resorption acitivity
All-trans retinoic-acid inhibits heterodimeric bone morphogenetic protein 2/7-stimulated osteoclastogenesis, and resorption acitivity
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全反式视黄酸抑制异二聚体骨形态发生蛋白 2/7 刺激的破骨细胞生成和吸收活性
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Gang Wu
中科院分区：
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作者：
Wenjuan Bi;Yi Liu;Jing Guo;Zhen Lin;Jinsong Liu;Miao Zhou;Daniel Wismeijer;Janak L.Pathak;Gang Wu
背景资料：骨再生异源二聚体骨形态发生蛋白2/7（BMP 2/7）促进破骨细胞生成，而全反式维甲酸（ATRA）抑制破骨细胞生成。然而，ATRA对生理性和/或BMP 2/7诱导的破骨细胞生成的影响尚不清楚。本研究旨在检测BMP 2/7和ATRA联合治疗对破骨细胞生成和骨吸收活性的影响。结果如下：将全反式视黄酸（1 µM）± BMP 2/7（5或50 ng/ml）加入小鼠前破骨细胞系RAW 264.7或小鼠骨髓源性巨噬细胞（BMM）培养物中。分析破骨细胞标志物基因表达、骨形成、断裂和再吸收活性。BMP 2/7强烈增强破骨细胞标记基因表达、破骨细胞生成和再吸收活性。有趣的是，ATRA完全抑制破骨细胞的形成，在存在或不存在BMP 2/7。维甲酸受体（RAR）的泛拮抗剂和RARα、β或γ的拮抗剂均不能逆转ATRA对破骨细胞生成的抑制作用。ATRA强烈抑制Rank和Nfatc 1表达。结论：全反式维甲酸抑制BMP 2/7诱导的破骨细胞生成和骨吸收活性可能通过RANKL-RANK途径实现。我们的研究结果表明，ATRA和BMP 2/7的联合应用可能是一种治疗破骨细胞过度活跃引起的骨丢失的新方法，如炎症引起的严重骨质疏松症和癌症骨转移引起的骨丢失。
Background: Bone regenerative heterodimeric bone morphogenetic protein 2/7 (BMP2/7) enhances but all-trans.retinoic acid (ATRA) inhibits osteoclastogenesis. However, the effect of ATRA on physiological and/or BMP2/7-induced.osteoclastogenesis in still unclear. In this study, we aimed to test the effect of combined treatment of BMP2/7 and.ATRA on osteoclastogenesis, and resorption activity..Results: All-trans retinoic acid (1 µM) ± BMP2/7 (5 or 50 ng/ml) was added in murine pre-osteoclasts cell line.RAW264.7 or mouse bone marrow derived macrophages (BMM) cultures. Osteoclast marker gene expression, osteo-.clastogenesis, and resorption activity were analyzed. BMP2/7 robustly enhanced osteoclast maker gene expression,.osteoclastogenesis, and resorption activity. Interestingly, ATRA completely inhibited osteoclast formation in presence.or absence of BMP2/7. Pan-antagonist of retinoic acid receptors (RARs) and antagonist of RARα, β or γ failed to reverse.the inhibitory effect of ATRA on osteoclastogenesis. ATRA strongly inhibited Rank and Nfatc1 expression..Conclusions: All-trans retinoic acid inhibits BMP2/7-induced osteoclastogenesis, and resorption activity possibly via.RANKL–RANK pathway. Our findings from previous and current study suggest that combination of ATRA and BMP2/7.could be a novel approach to treat hyperactive osteoclast-induced bone loss such as in inflammation-induced severe.osteoporosis and bone loss caused by cancer metastasis to bone.