All-trans retinoic-acid inhibits heterodimeric bone morphogenetic protein 2/7-stimulated osteoclastogenesis, and resorption activity

Cell & Bioscience

Daniel Wismeijer¹  Gang Wu¹  Zhen Lin²  Yi Liu³  Janak L. Pathak³  Jing Guo³  Miao Zhou³  Jinsong Liu⁴  Wenjuan Bi⁵ 

[1] Department of Oral Implantology and Prosthetic Dentistry, Academic Centre of Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam;Department of Orthopedics, The First Affiliated Hospital of Jinan University;Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Affiliated Stomatology Hospital of Guangzhou Medical University;School and Hospital of Stomatology, Wenzhou Medical University;School of Stomatology, North China University of Science and Technology;

关键词: Heterodimeric bone morphogenetic protein 2/7;    All-trans retinoic acid;    Osteoclastogenesis;    Osteoclast activity;    Bone loss;    Bone regeneration;   

DOI  :  10.1186/s13578-018-0246-y

来源: DOAJ

【 摘 要 】

Abstract 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, osteoclastogenesis, 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.

【 授权许可】

Unknown