Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784895332811800576 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9959662 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT huanglei mir199a5preduceschondrocytehypertrophyandattenuatesosteoarthritisprogressionviatheindianhedgehogsignalpathway AT jinmeng mir199a5preduceschondrocytehypertrophyandattenuatesosteoarthritisprogressionviatheindianhedgehogsignalpathway AT guruiying mir199a5preduceschondrocytehypertrophyandattenuatesosteoarthritisprogressionviatheindianhedgehogsignalpathway AT xiaokunlin mir199a5preduceschondrocytehypertrophyandattenuatesosteoarthritisprogressionviatheindianhedgehogsignalpathway AT lumengnan mir199a5preduceschondrocytehypertrophyandattenuatesosteoarthritisprogressionviatheindianhedgehogsignalpathway AT huoxinyu mir199a5preduceschondrocytehypertrophyandattenuatesosteoarthritisprogressionviatheindianhedgehogsignalpathway AT sunmengyao mir199a5preduceschondrocytehypertrophyandattenuatesosteoarthritisprogressionviatheindianhedgehogsignalpathway AT yangzhi mir199a5preduceschondrocytehypertrophyandattenuatesosteoarthritisprogressionviatheindianhedgehogsignalpathway AT wangzhiyuan mir199a5preduceschondrocytehypertrophyandattenuatesosteoarthritisprogressionviatheindianhedgehogsignalpathway AT zhangweijie mir199a5preduceschondrocytehypertrophyandattenuatesosteoarthritisprogressionviatheindianhedgehogsignalpathway AT zhiliqiang mir199a5preduceschondrocytehypertrophyandattenuatesosteoarthritisprogressionviatheindianhedgehogsignalpathway AT mengziang mir199a5preduceschondrocytehypertrophyandattenuatesosteoarthritisprogressionviatheindianhedgehogsignalpathway AT majie mir199a5preduceschondrocytehypertrophyandattenuatesosteoarthritisprogressionviatheindianhedgehogsignalpathway AT majianbing mir199a5preduceschondrocytehypertrophyandattenuatesosteoarthritisprogressionviatheindianhedgehogsignalpathway AT zhangrui mir199a5preduceschondrocytehypertrophyandattenuatesosteoarthritisprogressionviatheindianhedgehogsignalpathway |