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CircHmbox1 Targeting miRNA-1247-5p Is Involved in the Regulation of Bone Metabolism by TNF-α in Postmenopausal Osteoporosis
Tumor necrosis factor-alpha (TNF-α) 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 c...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786182/ https://www.ncbi.nlm.nih.gov/pubmed/33425899 http://dx.doi.org/10.3389/fcell.2020.594785 |
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author | Liu, Zhuochao Li, Changwei Huang, Ping Hu, Fangqiong Jiang, Min Xu, Xing Li, Bin Deng, Lianfu Ye, Tianwen Guo, Lei |
author_facet | Liu, Zhuochao Li, Changwei Huang, Ping Hu, Fangqiong Jiang, Min Xu, Xing Li, Bin Deng, Lianfu Ye, Tianwen Guo, Lei |
author_sort | Liu, Zhuochao |
collection | PubMed |
description | Tumor necrosis factor-alpha (TNF-α) 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-α-regulated osteoclasts differentiation and osteoblasts differentiation in PMOP. QRT-PCR was applied to detect expression of circRNA-circHmbox1 and miR-1247-5p in TNF-α-induced osteoclasts differentiation. Western blot, TRAP staining, alkaline phosphatase staining, alizarin red S staining, transwell and cell transfection were conducted to confirm that TNF-α 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-α-induced osteoclast formation in vivo and in vitro. CircHmbox1 could inhibit RANKL-induced osteoclasts differentiation primarily through binding to microRNA-1247-5p. TNF-α 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-α in PMOP. |
format | Online Article Text |
id | pubmed-7786182 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77861822021-01-07 CircHmbox1 Targeting miRNA-1247-5p Is Involved in the Regulation of Bone Metabolism by TNF-α in Postmenopausal Osteoporosis Liu, Zhuochao Li, Changwei Huang, Ping Hu, Fangqiong Jiang, Min Xu, Xing Li, Bin Deng, Lianfu Ye, Tianwen Guo, Lei Front Cell Dev Biol Cell and Developmental Biology Tumor necrosis factor-alpha (TNF-α) 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-α-regulated osteoclasts differentiation and osteoblasts differentiation in PMOP. QRT-PCR was applied to detect expression of circRNA-circHmbox1 and miR-1247-5p in TNF-α-induced osteoclasts differentiation. Western blot, TRAP staining, alkaline phosphatase staining, alizarin red S staining, transwell and cell transfection were conducted to confirm that TNF-α 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-α-induced osteoclast formation in vivo and in vitro. CircHmbox1 could inhibit RANKL-induced osteoclasts differentiation primarily through binding to microRNA-1247-5p. TNF-α 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-α in PMOP. Frontiers Media S.A. 2020-12-23 /pmc/articles/PMC7786182/ /pubmed/33425899 http://dx.doi.org/10.3389/fcell.2020.594785 Text en Copyright © 2020 Liu, Li, Huang, Hu, Jiang, Xu, Li, Deng, Ye and Guo. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Liu, Zhuochao Li, Changwei Huang, Ping Hu, Fangqiong Jiang, Min Xu, Xing Li, Bin Deng, Lianfu Ye, Tianwen Guo, Lei CircHmbox1 Targeting miRNA-1247-5p Is Involved in the Regulation of Bone Metabolism by TNF-α in Postmenopausal Osteoporosis |
title | CircHmbox1 Targeting miRNA-1247-5p Is Involved in the Regulation of Bone Metabolism by TNF-α in Postmenopausal Osteoporosis |
title_full | CircHmbox1 Targeting miRNA-1247-5p Is Involved in the Regulation of Bone Metabolism by TNF-α in Postmenopausal Osteoporosis |
title_fullStr | CircHmbox1 Targeting miRNA-1247-5p Is Involved in the Regulation of Bone Metabolism by TNF-α in Postmenopausal Osteoporosis |
title_full_unstemmed | CircHmbox1 Targeting miRNA-1247-5p Is Involved in the Regulation of Bone Metabolism by TNF-α in Postmenopausal Osteoporosis |
title_short | CircHmbox1 Targeting miRNA-1247-5p Is Involved in the Regulation of Bone Metabolism by TNF-α in Postmenopausal Osteoporosis |
title_sort | circhmbox1 targeting mirna-1247-5p is involved in the regulation of bone metabolism by tnf-α in postmenopausal osteoporosis |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786182/ https://www.ncbi.nlm.nih.gov/pubmed/33425899 http://dx.doi.org/10.3389/fcell.2020.594785 |
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