Estrogen inhibits osteoclasts formation and bone resorption via microRNA-27a targeting PPARγ and APC.

Abstract

Inhibition of osteoclasts formation and bone resorption by estrogen is very important in the etiology of postmenopausal osteoporosis. The mechanisms of this process are still not fully understood. Recent studies implicated an important role of microRNAs in estrogen-mediated responses in various cellular processes, including cell differentiation and proliferation. Thus, we hypothesized that these regulatory molecules might be implicated in the process of estrogen-decreased osteoclasts formation and bone resorption. Western blot, quantitative real-time polymerase chain reaction, tartrate-resistant acid phosphatase staining, pit formation assay and luciferase assay were used to investigate the role of microRNAs in estrogen-inhibited osteoclast differentiation and bone resorption. We found that estrogen could directly suppress receptor activator of nuclear factor B ligand/macrophage colony-stimulating factor-induced differentiation of bone marrow-derived macrophages into osteoclasts in the absence of stromal cell. MicroRNA-27a was significantly increased during the process of estrogen-decreased osteoclast differentiation. Overexpressing of microRNA-27a remarkably enhanced the inhibitory effect of estrogen on osteoclast differentiation and bone resorption, whereas which were alleviated by microRNA-27a depletion. Mechanistic studies showed that microRNA-27a inhibited peroxisome proliferator-activated receptor gamma (PPARγ) and adenomatous polyposis coli (APC) expression in osteoclasts through a microRNA-27a binding site within the 3'-untranslational region of PPARγ and APC. PPARγ and APC respectively contributed to microRNA-27a-decreased osteoclast differentiation and bone resorption. Taken together, these results showed that microRNA-27a may play a significant role in the process of estrogen-inhibited osteoclast differentiation and function.

• Authors: Lei Guo, Kaizhe Chen, Jun Yuan, Ping Huang, Xing Xu, Changwei Li, Niandong Qian, Jin Qi, Zhiliang Shao, Lianfu Deng, Chuan He, Jiping Xu
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 234 Issue 1 Pg. 581-594 (01 2018) ISSN: 1097-4652 [Electronic] United States
• PMID: 30272823 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Adenomatous Polyposis Coli Protein
• Estrogens
• MicroRNAs
• Mirn27 microRNA, mouse
• NF-kappa B
• PPAR gamma
• RANK Ligand
• adenomatous polyposis coli protein, mouse
• Macrophage Colony-Stimulating Factor

Topics

• Adenomatous Polyposis Coli (genetics, pathology)
• Adenomatous Polyposis Coli Protein (genetics)
• Animals
• Bone Marrow Cells (metabolism)
• Bone Resorption (genetics, pathology)
• Cell Differentiation (genetics)
• Cell Proliferation (genetics)
• Estrogens (genetics, metabolism)
• Macrophage Colony-Stimulating Factor
• Mice
• MicroRNAs (genetics)
• NF-kappa B (genetics)
• Osteoclasts (metabolism, pathology)
• PPAR gamma (genetics)
• RANK Ligand (genetics)