CircRNA_28313/miR-195a/CSF1 axis modulates osteoclast differentiation to affect OVX-induced bone absorption in mice

• Published in: RNA biology 2019-09, Vol.16 (9), p.1249-1262
• Main Authors: Chen, Xia, Ouyang, Zhengxiao, Shen, Yi, Liu, Bo, Zhang, Qiang, Wan, Lu, Yin, Ziqing, Zhu, Wei, Li, Shuai, Peng, Dan
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; Animals; Base Sequence; bioinformatics; Bone absorption; bone formation; bone marrow; Bone Marrow Cells - metabolism; bone resorption; Bone Resorption - genetics; Bone Resorption - pathology; cell differentiation; Cell Differentiation - genetics; circRNA_28313; circular RNA; CSF1; Disease Models, Animal; gene expression regulation; HEK293 Cells; homeostasis; Humans; macrophage colony-stimulating factor; Macrophage Colony-Stimulating Factor - metabolism; macrophages; Macrophages - metabolism; mice; Mice, Inbred C57BL; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; miR-195a; monocytes; non-coding RNA; osteoclast; osteoclasts; Osteoclasts - metabolism; Osteoclasts - pathology; Osteoporosis - genetics; Osteoporosis - pathology; Ovariectomy; Research Paper; RNA, Circular - genetics; RNA, Circular - metabolism
• ISSN: 1547-6286; 1555-8584; 1555-8584
• DOI: 10.1080/15476286.2019.1624470

Osteoblastic bone formation and osteoclastic bone resorption dynamically maintain the bone homeostasis; in the present study, we attempt to investigate the mechanism of the excessive activation of osteoclasts inducing the deregulation of bone homeostasis from the perspective of non-coding RNA regulation. Differentially expressed patterns of circRNAs were examined in non-treated and RANKL + CSF1-treated bone marrow monocyte/macrophage (BMM) cells and differentially-expressed miRNAs during osteoclast differentiation were analyzed and identified. We found that circRNA_28313 was significantly induced by RANKL + CSF1 treatment. circRNA_28313 knockdown significantly inhibited RANKL + CSF1-induced differentiation of osteoclasts within BMM cells in vitro, while suppressed ovariectomized (OVX)-induced bone resorption in mice in vivo. Via bioinformatics analyses, it has been demonstrated that miR-195a might bind to circRNA_28313 and CSF1 and together form a circRNA-miRNA-mRNA network. circRNA_28313 relieves miR-195a-mediated suppression on CSF1 via acting as a ceRNA, therefore modulating the osteoclast differentiation in BMM cells. In conclusion, circRNA_28313, miR-195a, and CSF1 form a ceRNA network to function in RANKL + CSF1-induced osteoclast differentiation, thus affecting OVX-induced bone absorption in mice.