PMID- 33425899 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210112 IS - 2296-634X (Print) IS - 2296-634X (Electronic) IS - 2296-634X (Linking) VI - 8 DP - 2020 TI - CircHmbox1 Targeting miRNA-1247-5p Is Involved in the Regulation of Bone Metabolism by TNF-alpha in Postmenopausal Osteoporosis. PG - 594785 LID - 10.3389/fcell.2020.594785 [doi] LID - 594785 AB - Tumor necrosis factor-alpha (TNF-alpha) promotes osteoclasts differentiation to enhance bone resorption and inhibits osteoblasts differentiation to impair bone formation, which plays a central role in the development of postmenopausal osteoporosis (PMOP). Recent studies implicated an important role of circular RNAs (circRNAs) in osteoporosis. The purpose of this study is to investigate whether circRNAs might be implicated in TNF-alpha-regulated osteoclasts differentiation and osteoblasts differentiation in PMOP. QRT-PCR was applied to detect expression of circRNA-circHmbox1 and miR-1247-5p in TNF-alpha-induced osteoclasts differentiation. Western blot, TRAP staining, alkaline phosphatase staining, alizarin red S staining, transwell and cell transfection were conducted to confirm that TNF-alpha inhibited osteoblasts differentiation by exosomal with low circHmbox1 expression from osteoclasts. Bioinformatics analysis and luciferase reporter revealed the mechanisms of the circHmbox1/miR-1247-5p/B cell lymphoma 6 (Bcl6) interaction. In this study, we found that the level of circRNA-circHmbox1 was obviously reduced in TNF-alpha-induced osteoclast formation in vivo and in vitro. CircHmbox1 could inhibit RANKL-induced osteoclasts differentiation primarily through binding to microRNA-1247-5p. TNF-alpha decreased osteoblasts differentiation by exosomal with low circHmbox1 expression from osteoclasts. Mechanistic studies showed that microRNA-1247-5p regulated osteoclasts differentiation and osteoblasts differentiation by targeting Bcl6, which was confirmed to play opposite roles in osteoblasts differentiation and osteoclasts differentiation. Our results provide evidence that circHmbox1-targeting miR-1247-5p is involved in the regulation of bone metabolisms by TNF-alpha in PMOP. CI - Copyright (c) 2020 Liu, Li, Huang, Hu, Jiang, Xu, Li, Deng, Ye and Guo. FAU - Liu, Zhuochao AU - Liu Z AD - Department of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Li, Changwei AU - Li C AD - Department of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Huang, Ping AU - Huang P AD - Department of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Hu, Fangqiong AU - Hu F AD - Department of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Jiang, Min AU - Jiang M AD - Department of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Xu, Xing AU - Xu X AD - Department of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Li, Bin AU - Li B AD - Department of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Deng, Lianfu AU - Deng L AD - Department of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Ye, Tianwen AU - Ye T AD - Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China. FAU - Guo, Lei AU - Guo L AD - Department of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. LA - eng PT - Journal Article DEP - 20201223 PL - Switzerland TA - Front Cell Dev Biol JT - Frontiers in cell and developmental biology JID - 101630250 PMC - PMC7786182 OTO - NOTNLM OT - B cell lymphoma 6 OT - TNF-alpha OT - circHmbox1 OT - microRNA-1247-5p OT - postmenopausal osteoporosis COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/01/12 06:00 MHDA- 2021/01/12 06:01 PMCR- 2020/01/01 CRDT- 2021/01/11 05:42 PHST- 2020/08/14 00:00 [received] PHST- 2020/12/07 00:00 [accepted] PHST- 2021/01/11 05:42 [entrez] PHST- 2021/01/12 06:00 [pubmed] PHST- 2021/01/12 06:01 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fcell.2020.594785 [doi] PST - epublish SO - Front Cell Dev Biol. 2020 Dec 23;8:594785. doi: 10.3389/fcell.2020.594785. eCollection 2020.