Overexpression of miR125b Promotes Osteoporosis Through miR-125b-TRAF6 Pathway in Postmenopausal Ovariectomized Rats

Gang Wang, Lecheng Zhang, Chao Yan, Fengbin Wang, Yuelei Zhang Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, 230000, People’s Republic of ChinaCorrespondence: Yuelei ZhangDepartment of Orthopedics, The First Affiliated Hospital of Anhui Medica...

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Autores principales:	Wang G, Zhang L, Yan C, Wang F, Zhang Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	mir‐125b osteoporosis traf6 jak2/stat3 pathway Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/86dc1b57d03a4454a986b5be0b3211ac
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spelling	oai:doaj.org-article:86dc1b57d03a4454a986b5be0b3211ac2021-12-02T12:17:46ZOverexpression of miR125b Promotes Osteoporosis Through miR-125b-TRAF6 Pathway in Postmenopausal Ovariectomized Rats1178-7007https://doaj.org/article/86dc1b57d03a4454a986b5be0b3211ac2021-02-01T00:00:00Zhttps://www.dovepress.com/overexpression-of-mir125b-promotes-osteoporosis-through-mir-125b-traf6-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Gang Wang, Lecheng Zhang, Chao Yan, Fengbin Wang, Yuelei Zhang Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, 230000, People’s Republic of ChinaCorrespondence: Yuelei ZhangDepartment of Orthopedics, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230000, People’s Republic of ChinaTel/Fax +86-551-62922065Email yuelei.zhang2001@hotmail.comBackground: Postmenopausal osteoporosis is one of the most common types of osteoporosis that women suffer from. Studies involving molecular mechanisms for designing better therapeutic strategies for postmenopausal osteoporosis are still rare. The present study investigates the role of miR-125b in postmenopausal osteoporosis.Methods: Microarray analysis was done to screen the gene database. Tissue samples of postmenopausal women were collected to study the miRNA profiles. MC3T3-E1 cells were used and were submitted for transfection. CCK-8 assay was done to check the viability of cells, whereas toxicity was done by lactate dehydrogenase assay kit. TargetScan was done to target genes of miR-125b followed by confirmation by Luciferase reporter assay. For animal studies a rat model of ovariectomized rats was created. Bone mineral density and biomechanics were measured by densitometer. The mRNA levels were assessed by qRT-PCR and proteins by Western blot assay.Results: miR-125b was over-expressed in human osteoporosis samples. In vitro studies suggested that miR-125b suppressed the cell viability and promoted release of LDH, it also enhanced the RANKL/OPG ratio and suppressed levels of BMP2 and Runx2. Bioinformatics identified TRAF6 as a potential target of miR-125b, further confirmed by luciferase assay, also miR-125b negatively regulated the levels of TRAF6 gene in osteoporosis bones involving the JAK2/STAT3 cascade. In the rat model, miR-125b decreased the bone mineral density and biomechanical parameters in bones by altering the TRAF6 gene involving the JAK2/STAT3 pathway.Conclusion: The outcomes suggested that miR-125b was responsible for the development of postmenopausal osteoporosis and promoted its progression by the TRAF6 gene via the JAK2/STAT3 pathway.Keywords: miR‐125b, osteoporosis, TRAF6, JAK2/STAT3 pathwayWang GZhang LYan CWang FZhang YDove Medical Pressarticlemir‐125bosteoporosistraf6jak2/stat3 pathwaySpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 671-682 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mir‐125b osteoporosis traf6 jak2/stat3 pathway Specialties of internal medicine RC581-951
spellingShingle	mir‐125b osteoporosis traf6 jak2/stat3 pathway Specialties of internal medicine RC581-951 Wang G Zhang L Yan C Wang F Zhang Y Overexpression of miR125b Promotes Osteoporosis Through miR-125b-TRAF6 Pathway in Postmenopausal Ovariectomized Rats
description	Gang Wang, Lecheng Zhang, Chao Yan, Fengbin Wang, Yuelei Zhang Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, 230000, People’s Republic of ChinaCorrespondence: Yuelei ZhangDepartment of Orthopedics, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230000, People’s Republic of ChinaTel/Fax +86-551-62922065Email yuelei.zhang2001@hotmail.comBackground: Postmenopausal osteoporosis is one of the most common types of osteoporosis that women suffer from. Studies involving molecular mechanisms for designing better therapeutic strategies for postmenopausal osteoporosis are still rare. The present study investigates the role of miR-125b in postmenopausal osteoporosis.Methods: Microarray analysis was done to screen the gene database. Tissue samples of postmenopausal women were collected to study the miRNA profiles. MC3T3-E1 cells were used and were submitted for transfection. CCK-8 assay was done to check the viability of cells, whereas toxicity was done by lactate dehydrogenase assay kit. TargetScan was done to target genes of miR-125b followed by confirmation by Luciferase reporter assay. For animal studies a rat model of ovariectomized rats was created. Bone mineral density and biomechanics were measured by densitometer. The mRNA levels were assessed by qRT-PCR and proteins by Western blot assay.Results: miR-125b was over-expressed in human osteoporosis samples. In vitro studies suggested that miR-125b suppressed the cell viability and promoted release of LDH, it also enhanced the RANKL/OPG ratio and suppressed levels of BMP2 and Runx2. Bioinformatics identified TRAF6 as a potential target of miR-125b, further confirmed by luciferase assay, also miR-125b negatively regulated the levels of TRAF6 gene in osteoporosis bones involving the JAK2/STAT3 cascade. In the rat model, miR-125b decreased the bone mineral density and biomechanical parameters in bones by altering the TRAF6 gene involving the JAK2/STAT3 pathway.Conclusion: The outcomes suggested that miR-125b was responsible for the development of postmenopausal osteoporosis and promoted its progression by the TRAF6 gene via the JAK2/STAT3 pathway.Keywords: miR‐125b, osteoporosis, TRAF6, JAK2/STAT3 pathway
format	article
author	Wang G Zhang L Yan C Wang F Zhang Y
author_facet	Wang G Zhang L Yan C Wang F Zhang Y
author_sort	Wang G
title	Overexpression of miR125b Promotes Osteoporosis Through miR-125b-TRAF6 Pathway in Postmenopausal Ovariectomized Rats
title_short	Overexpression of miR125b Promotes Osteoporosis Through miR-125b-TRAF6 Pathway in Postmenopausal Ovariectomized Rats
title_full	Overexpression of miR125b Promotes Osteoporosis Through miR-125b-TRAF6 Pathway in Postmenopausal Ovariectomized Rats
title_fullStr	Overexpression of miR125b Promotes Osteoporosis Through miR-125b-TRAF6 Pathway in Postmenopausal Ovariectomized Rats
title_full_unstemmed	Overexpression of miR125b Promotes Osteoporosis Through miR-125b-TRAF6 Pathway in Postmenopausal Ovariectomized Rats
title_sort	overexpression of mir125b promotes osteoporosis through mir-125b-traf6 pathway in postmenopausal ovariectomized rats
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/86dc1b57d03a4454a986b5be0b3211ac
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Overexpression of miR125b Promotes Osteoporosis Through miR-125b-TRAF6 Pathway in Postmenopausal Ovariectomized Rats

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