MiR-23b-3p promotes postmenopausal osteoporosis by targeting MRC2 and regulating the Wnt/β-catenin signaling pathway

Postmenopausal osteoporosis (PMOP) is one of the most common metabolic bone diseases in postmenopausal women. Increasing evidence has indicated that microRNAs (miRNAs) play vital regulatory roles during osteoporosis progression. This study aimed to investigate the potential function of miR-23b-3p in...

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Main Authors: Ran Li, Qing Ruan, Fei Yin, Kunchi Zhao
Format: Article
Language:English
Published: Elsevier 2021-01-01
Series:Journal of Pharmacological Sciences
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861320301109
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author Ran Li
Qing Ruan
Fei Yin
Kunchi Zhao
author_facet Ran Li
Qing Ruan
Fei Yin
Kunchi Zhao
author_sort Ran Li
collection DOAJ
description Postmenopausal osteoporosis (PMOP) is one of the most common metabolic bone diseases in postmenopausal women. Increasing evidence has indicated that microRNAs (miRNAs) play vital regulatory roles during osteoporosis progression. This study aimed to investigate the potential function of miR-23b-3p in the osteogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs). PMOP was induced in mice by bilateral ovariectomy. X-ray absorptiometry was applied to detect BMD and BMC in PMOP mice. Luciferase reporter assay and RIP assay were utilized to investigate the relationship between miR-23b-3p and MRC2. We found the upregulation of miR-23b-3p in bone tissues of PMOP mice. Silencing of miR-23b-3p relieved PMOP in mice. Moreover, miR-23b-3p knockdown facilitated the osteogenic differentiation of hMSCs by increasing the expression of Runx2, OCN, Osterix and promoting ALP activity. Mechanistically, MRC2 is a downstream target gene of miR-23b-3p. MRC2 knockdown significantly rescued the promoting effect of lenti-miR-23b-3p inhibitor on osteogenic differentiation of hMSCs. Furthermore, miR-23b-3p targeted MRC2 to inhibit the Wnt/β-catenin pathway during the osteogenic differentiation of hMSCs. In summary, inhibition of miR-23b-3p alleviates PMOP by targeting MRC2 to inhibit the Wnt/β-catenin signaling, which may provide a novel molecular insight for osteoporosis therapy.
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spelling doaj.art-8c16450f8c8e49d8b32622fd09ca57d92022-12-21T23:20:04ZengElsevierJournal of Pharmacological Sciences1347-86132021-01-0114516978MiR-23b-3p promotes postmenopausal osteoporosis by targeting MRC2 and regulating the Wnt/β-catenin signaling pathwayRan Li0Qing Ruan1Fei Yin2Kunchi Zhao3Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, ChinaDepartment of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, ChinaDepartment of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, ChinaCorresponding author. China-Japan Union Hospital of Jilin University, No.126 Xiantai Street, Changchun, Jilin, China.; Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, ChinaPostmenopausal osteoporosis (PMOP) is one of the most common metabolic bone diseases in postmenopausal women. Increasing evidence has indicated that microRNAs (miRNAs) play vital regulatory roles during osteoporosis progression. This study aimed to investigate the potential function of miR-23b-3p in the osteogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs). PMOP was induced in mice by bilateral ovariectomy. X-ray absorptiometry was applied to detect BMD and BMC in PMOP mice. Luciferase reporter assay and RIP assay were utilized to investigate the relationship between miR-23b-3p and MRC2. We found the upregulation of miR-23b-3p in bone tissues of PMOP mice. Silencing of miR-23b-3p relieved PMOP in mice. Moreover, miR-23b-3p knockdown facilitated the osteogenic differentiation of hMSCs by increasing the expression of Runx2, OCN, Osterix and promoting ALP activity. Mechanistically, MRC2 is a downstream target gene of miR-23b-3p. MRC2 knockdown significantly rescued the promoting effect of lenti-miR-23b-3p inhibitor on osteogenic differentiation of hMSCs. Furthermore, miR-23b-3p targeted MRC2 to inhibit the Wnt/β-catenin pathway during the osteogenic differentiation of hMSCs. In summary, inhibition of miR-23b-3p alleviates PMOP by targeting MRC2 to inhibit the Wnt/β-catenin signaling, which may provide a novel molecular insight for osteoporosis therapy.http://www.sciencedirect.com/science/article/pii/S1347861320301109miR-23b-3pMRC2Wnt/β-catenin pathwayPostmenopausal osteoporosis
spellingShingle Ran Li
Qing Ruan
Fei Yin
Kunchi Zhao
MiR-23b-3p promotes postmenopausal osteoporosis by targeting MRC2 and regulating the Wnt/β-catenin signaling pathway
Journal of Pharmacological Sciences
miR-23b-3p
MRC2
Wnt/β-catenin pathway
Postmenopausal osteoporosis
title MiR-23b-3p promotes postmenopausal osteoporosis by targeting MRC2 and regulating the Wnt/β-catenin signaling pathway
title_full MiR-23b-3p promotes postmenopausal osteoporosis by targeting MRC2 and regulating the Wnt/β-catenin signaling pathway
title_fullStr MiR-23b-3p promotes postmenopausal osteoporosis by targeting MRC2 and regulating the Wnt/β-catenin signaling pathway
title_full_unstemmed MiR-23b-3p promotes postmenopausal osteoporosis by targeting MRC2 and regulating the Wnt/β-catenin signaling pathway
title_short MiR-23b-3p promotes postmenopausal osteoporosis by targeting MRC2 and regulating the Wnt/β-catenin signaling pathway
title_sort mir 23b 3p promotes postmenopausal osteoporosis by targeting mrc2 and regulating the wnt β catenin signaling pathway
topic miR-23b-3p
MRC2
Wnt/β-catenin pathway
Postmenopausal osteoporosis
url http://www.sciencedirect.com/science/article/pii/S1347861320301109
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AT feiyin mir23b3ppromotespostmenopausalosteoporosisbytargetingmrc2andregulatingthewntbcateninsignalingpathway
AT kunchizhao mir23b3ppromotespostmenopausalosteoporosisbytargetingmrc2andregulatingthewntbcateninsignalingpathway