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MiR-218-5p-dependent SOCS3 downregulation increases osteoblast differentiation inpostmenopausal osteoporosis
BACKGROUND: Postmenopausal osteoporosis (POP) is a prevalent skeletal disease among elderly women. Previous study indicated that suppressor of cytokine signaling 3 (SOCS3) participates in the regulation of bone marrow stromal cell (BMSC) osteogenesis. Here, we further investigated the exact function...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9930297/ https://www.ncbi.nlm.nih.gov/pubmed/36793115 http://dx.doi.org/10.1186/s13018-023-03580-4 |
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author | Zhou, Qian Zhou, Lihua Li, Jun |
author_facet | Zhou, Qian Zhou, Lihua Li, Jun |
author_sort | Zhou, Qian |
collection | PubMed |
description | BACKGROUND: Postmenopausal osteoporosis (POP) is a prevalent skeletal disease among elderly women. Previous study indicated that suppressor of cytokine signaling 3 (SOCS3) participates in the regulation of bone marrow stromal cell (BMSC) osteogenesis. Here, we further investigated the exact function and mechanism of SOCS3 in POP progression. METHODS: BMSCs were isolated from Sprague–Dawley rats and treated with Dexamethasone (Dex). Alizarin Red staining and ALP activity assays were applied to assess the osteogenic differentiation of rat BMSCs under the indicated conditions. Osteogenic genes (ALP, OPN, OCN, COL1) mRNA levels were determined using quantitative RT-PCR. Luciferase reporter assay verified the interaction between SOCS3 and miR-218-5p. Rat models of POP were established in ovariectomized (OVX) rats to detect the in vivo effects of SOCS3 and miR-218-5p. RESULTS: We found that silencing SOCS3 antagonized the suppressive effects of Dex on the osteogenic differentiation of BMSCs. SOCS3 was found to be targeted by miR-218-5p in BMSCs. The SOCS3 levels were negatively modulated by miR-218-5p in femurs of POP rats. MiR-218-5p upregulation promoted the BMSC osteogenic differentiation, while SOCS3 overexpression reversed the effects of miR-218-5p. Moreover, SOCS3 was highly expressed and miR-218-5p was downregulated in the OVX rat models, and silencing SOCS3 or overexpressing miR-218-5p alleviated POP in OVX rats by promoting osteogenesis. CONCLUSION: SOCS3 downregulation mediated by miR-218-5p increases osteoblast differentiation to alleviate POP. |
format | Online Article Text |
id | pubmed-9930297 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-99302972023-02-16 MiR-218-5p-dependent SOCS3 downregulation increases osteoblast differentiation inpostmenopausal osteoporosis Zhou, Qian Zhou, Lihua Li, Jun J Orthop Surg Res Research Article BACKGROUND: Postmenopausal osteoporosis (POP) is a prevalent skeletal disease among elderly women. Previous study indicated that suppressor of cytokine signaling 3 (SOCS3) participates in the regulation of bone marrow stromal cell (BMSC) osteogenesis. Here, we further investigated the exact function and mechanism of SOCS3 in POP progression. METHODS: BMSCs were isolated from Sprague–Dawley rats and treated with Dexamethasone (Dex). Alizarin Red staining and ALP activity assays were applied to assess the osteogenic differentiation of rat BMSCs under the indicated conditions. Osteogenic genes (ALP, OPN, OCN, COL1) mRNA levels were determined using quantitative RT-PCR. Luciferase reporter assay verified the interaction between SOCS3 and miR-218-5p. Rat models of POP were established in ovariectomized (OVX) rats to detect the in vivo effects of SOCS3 and miR-218-5p. RESULTS: We found that silencing SOCS3 antagonized the suppressive effects of Dex on the osteogenic differentiation of BMSCs. SOCS3 was found to be targeted by miR-218-5p in BMSCs. The SOCS3 levels were negatively modulated by miR-218-5p in femurs of POP rats. MiR-218-5p upregulation promoted the BMSC osteogenic differentiation, while SOCS3 overexpression reversed the effects of miR-218-5p. Moreover, SOCS3 was highly expressed and miR-218-5p was downregulated in the OVX rat models, and silencing SOCS3 or overexpressing miR-218-5p alleviated POP in OVX rats by promoting osteogenesis. CONCLUSION: SOCS3 downregulation mediated by miR-218-5p increases osteoblast differentiation to alleviate POP. BioMed Central 2023-02-15 /pmc/articles/PMC9930297/ /pubmed/36793115 http://dx.doi.org/10.1186/s13018-023-03580-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Zhou, Qian Zhou, Lihua Li, Jun MiR-218-5p-dependent SOCS3 downregulation increases osteoblast differentiation inpostmenopausal osteoporosis |
title | MiR-218-5p-dependent SOCS3 downregulation increases osteoblast differentiation inpostmenopausal osteoporosis |
title_full | MiR-218-5p-dependent SOCS3 downregulation increases osteoblast differentiation inpostmenopausal osteoporosis |
title_fullStr | MiR-218-5p-dependent SOCS3 downregulation increases osteoblast differentiation inpostmenopausal osteoporosis |
title_full_unstemmed | MiR-218-5p-dependent SOCS3 downregulation increases osteoblast differentiation inpostmenopausal osteoporosis |
title_short | MiR-218-5p-dependent SOCS3 downregulation increases osteoblast differentiation inpostmenopausal osteoporosis |
title_sort | mir-218-5p-dependent socs3 downregulation increases osteoblast differentiation inpostmenopausal osteoporosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9930297/ https://www.ncbi.nlm.nih.gov/pubmed/36793115 http://dx.doi.org/10.1186/s13018-023-03580-4 |
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