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miR-199a-5p Reduces Chondrocyte Hypertrophy and Attenuates Osteoarthritis Progression via the Indian Hedgehog Signal Pathway

Osteoarthritis (OA), the most common type of arthritis, is an age-associated disease, characterized by the progressive degradation of articular cartilage, synovial inflammation, and degeneration of subchondral bone. Chondrocyte proliferation is regulated by the Indian hedgehog (IHH in humans, Ihh in...

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Autores principales: Huang, Lei, Jin, Meng, Gu, Ruiying, Xiao, Kunlin, Lu, Mengnan, Huo, Xinyu, Sun, Mengyao, Yang, Zhi, Wang, Zhiyuan, Zhang, Weijie, Zhi, Liqiang, Meng, Ziang, Ma, Jie, Ma, Jianbing, Zhang, Rui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9959662/
https://www.ncbi.nlm.nih.gov/pubmed/36835852
http://dx.doi.org/10.3390/jcm12041313
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author Huang, Lei
Jin, Meng
Gu, Ruiying
Xiao, Kunlin
Lu, Mengnan
Huo, Xinyu
Sun, Mengyao
Yang, Zhi
Wang, Zhiyuan
Zhang, Weijie
Zhi, Liqiang
Meng, Ziang
Ma, Jie
Ma, Jianbing
Zhang, Rui
author_facet Huang, Lei
Jin, Meng
Gu, Ruiying
Xiao, Kunlin
Lu, Mengnan
Huo, Xinyu
Sun, Mengyao
Yang, Zhi
Wang, Zhiyuan
Zhang, Weijie
Zhi, Liqiang
Meng, Ziang
Ma, Jie
Ma, Jianbing
Zhang, Rui
author_sort Huang, Lei
collection PubMed
description Osteoarthritis (OA), the most common type of arthritis, is an age-associated disease, characterized by the progressive degradation of articular cartilage, synovial inflammation, and degeneration of subchondral bone. Chondrocyte proliferation is regulated by the Indian hedgehog (IHH in humans, Ihh in animals) signaling molecule, which regulates hypertrophy and endochondral ossification in the development of the skeletal system. microRNAs (miRNAs, miRs) are a family of about 22-nucleotide endogenous non-coding RNAs, which negatively regulate gene expression. In this study, the expression level of IHH was upregulated in the damaged articular cartilage tissues among OA patients and OA cell cultures, while that of miR-199a-5p was the opposite. Further investigations demonstrated that miR-199a-5p could directly regulate IHH expression and reduce chondrocyte hypertrophy and matrix degradation via the IHH signal pathway in the primary human chondrocytes. The intra-articular injection of synthetic miR-199a-5p agomir attenuated OA symptoms in rats, including the alleviation of articular cartilage destruction, subchondral bone degradation, and synovial inflammation. The miR-199a-5p agomir could also inhibit the Ihh signaling pathway in vivo. This study might help in understanding the role of miR-199a-5p in the pathophysiology and molecular mechanisms of OA and indicate a potential novel therapeutic strategy for OA patients.
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spelling pubmed-99596622023-02-26 miR-199a-5p Reduces Chondrocyte Hypertrophy and Attenuates Osteoarthritis Progression via the Indian Hedgehog Signal Pathway Huang, Lei Jin, Meng Gu, Ruiying Xiao, Kunlin Lu, Mengnan Huo, Xinyu Sun, Mengyao Yang, Zhi Wang, Zhiyuan Zhang, Weijie Zhi, Liqiang Meng, Ziang Ma, Jie Ma, Jianbing Zhang, Rui J Clin Med Article Osteoarthritis (OA), the most common type of arthritis, is an age-associated disease, characterized by the progressive degradation of articular cartilage, synovial inflammation, and degeneration of subchondral bone. Chondrocyte proliferation is regulated by the Indian hedgehog (IHH in humans, Ihh in animals) signaling molecule, which regulates hypertrophy and endochondral ossification in the development of the skeletal system. microRNAs (miRNAs, miRs) are a family of about 22-nucleotide endogenous non-coding RNAs, which negatively regulate gene expression. In this study, the expression level of IHH was upregulated in the damaged articular cartilage tissues among OA patients and OA cell cultures, while that of miR-199a-5p was the opposite. Further investigations demonstrated that miR-199a-5p could directly regulate IHH expression and reduce chondrocyte hypertrophy and matrix degradation via the IHH signal pathway in the primary human chondrocytes. The intra-articular injection of synthetic miR-199a-5p agomir attenuated OA symptoms in rats, including the alleviation of articular cartilage destruction, subchondral bone degradation, and synovial inflammation. The miR-199a-5p agomir could also inhibit the Ihh signaling pathway in vivo. This study might help in understanding the role of miR-199a-5p in the pathophysiology and molecular mechanisms of OA and indicate a potential novel therapeutic strategy for OA patients. MDPI 2023-02-07 /pmc/articles/PMC9959662/ /pubmed/36835852 http://dx.doi.org/10.3390/jcm12041313 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huang, Lei
Jin, Meng
Gu, Ruiying
Xiao, Kunlin
Lu, Mengnan
Huo, Xinyu
Sun, Mengyao
Yang, Zhi
Wang, Zhiyuan
Zhang, Weijie
Zhi, Liqiang
Meng, Ziang
Ma, Jie
Ma, Jianbing
Zhang, Rui
miR-199a-5p Reduces Chondrocyte Hypertrophy and Attenuates Osteoarthritis Progression via the Indian Hedgehog Signal Pathway
title miR-199a-5p Reduces Chondrocyte Hypertrophy and Attenuates Osteoarthritis Progression via the Indian Hedgehog Signal Pathway
title_full miR-199a-5p Reduces Chondrocyte Hypertrophy and Attenuates Osteoarthritis Progression via the Indian Hedgehog Signal Pathway
title_fullStr miR-199a-5p Reduces Chondrocyte Hypertrophy and Attenuates Osteoarthritis Progression via the Indian Hedgehog Signal Pathway
title_full_unstemmed miR-199a-5p Reduces Chondrocyte Hypertrophy and Attenuates Osteoarthritis Progression via the Indian Hedgehog Signal Pathway
title_short miR-199a-5p Reduces Chondrocyte Hypertrophy and Attenuates Osteoarthritis Progression via the Indian Hedgehog Signal Pathway
title_sort mir-199a-5p reduces chondrocyte hypertrophy and attenuates osteoarthritis progression via the indian hedgehog signal pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9959662/
https://www.ncbi.nlm.nih.gov/pubmed/36835852
http://dx.doi.org/10.3390/jcm12041313
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