Cargando…
Estrogen-related receptor γ is a novel catabolic regulator of osteoarthritis pathogenesis
Osteoarthritis (OA) is the most common form of arthritis and is a leading cause of disability with a large socioeconomic cost. OA is a whole-joint disease characterized by cartilage destruction, synovial inflammation, osteophyte formation, and subchondral bone sclerosis. To date, however, no effecti...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Society for Biochemistry and Molecular Biology
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933210/ https://www.ncbi.nlm.nih.gov/pubmed/29366446 http://dx.doi.org/10.5483/BMBRep.2018.51.4.019 |
_version_ | 1783319935220449280 |
---|---|
author | Son, Young-Ok Chun, Jang-Soo |
author_facet | Son, Young-Ok Chun, Jang-Soo |
author_sort | Son, Young-Ok |
collection | PubMed |
description | Osteoarthritis (OA) is the most common form of arthritis and is a leading cause of disability with a large socioeconomic cost. OA is a whole-joint disease characterized by cartilage destruction, synovial inflammation, osteophyte formation, and subchondral bone sclerosis. To date, however, no effective disease-modifying therapies for OA have been developed. The estrogen-related receptors (ERRs), a family of orphan nuclear receptor transcription factors, are composed of ERRα, ERRβ, and ERRγ, which play diverse biological functions such as cellular energy metabolism. However, the role of ERRs in OA pathogenesis has not been studied yet. Among the ERR family members, ERRγ is markedly upregulated in human and various models of mouse OA cartilage. Adenovirus-mediated overexpression of ERRγ in the mouse knee joint tissue caused OA pathogenesis. Additionally, cartilage-specific ERRγ transgenic (Tg) mice exhibited enhanced experimental OA. Consistently, ERRγ in articular chondrocytes directly caused expression of matrix metalloproteinase (MMP) 3 and MMP13, which play a crucial role in cartilage destruction. In contrast, genetic ablation of Esrrg or shRNA-mediated Esrrg silencing in the joint tissues abrogated experimental OA in mice. These results collectively indicated that ERRγ is a novel catabolic regulator of OA pathogenesis and can be used as a therapeutic target for OA. |
format | Online Article Text |
id | pubmed-5933210 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Korean Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-59332102018-05-08 Estrogen-related receptor γ is a novel catabolic regulator of osteoarthritis pathogenesis Son, Young-Ok Chun, Jang-Soo BMB Rep Perspective Osteoarthritis (OA) is the most common form of arthritis and is a leading cause of disability with a large socioeconomic cost. OA is a whole-joint disease characterized by cartilage destruction, synovial inflammation, osteophyte formation, and subchondral bone sclerosis. To date, however, no effective disease-modifying therapies for OA have been developed. The estrogen-related receptors (ERRs), a family of orphan nuclear receptor transcription factors, are composed of ERRα, ERRβ, and ERRγ, which play diverse biological functions such as cellular energy metabolism. However, the role of ERRs in OA pathogenesis has not been studied yet. Among the ERR family members, ERRγ is markedly upregulated in human and various models of mouse OA cartilage. Adenovirus-mediated overexpression of ERRγ in the mouse knee joint tissue caused OA pathogenesis. Additionally, cartilage-specific ERRγ transgenic (Tg) mice exhibited enhanced experimental OA. Consistently, ERRγ in articular chondrocytes directly caused expression of matrix metalloproteinase (MMP) 3 and MMP13, which play a crucial role in cartilage destruction. In contrast, genetic ablation of Esrrg or shRNA-mediated Esrrg silencing in the joint tissues abrogated experimental OA in mice. These results collectively indicated that ERRγ is a novel catabolic regulator of OA pathogenesis and can be used as a therapeutic target for OA. Korean Society for Biochemistry and Molecular Biology 2018-04 2018-04-30 /pmc/articles/PMC5933210/ /pubmed/29366446 http://dx.doi.org/10.5483/BMBRep.2018.51.4.019 Text en Copyright © 2018 by the The Korean Society for Biochemistry and Molecular Biology This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Perspective Son, Young-Ok Chun, Jang-Soo Estrogen-related receptor γ is a novel catabolic regulator of osteoarthritis pathogenesis |
title | Estrogen-related receptor γ is a novel catabolic regulator of osteoarthritis pathogenesis |
title_full | Estrogen-related receptor γ is a novel catabolic regulator of osteoarthritis pathogenesis |
title_fullStr | Estrogen-related receptor γ is a novel catabolic regulator of osteoarthritis pathogenesis |
title_full_unstemmed | Estrogen-related receptor γ is a novel catabolic regulator of osteoarthritis pathogenesis |
title_short | Estrogen-related receptor γ is a novel catabolic regulator of osteoarthritis pathogenesis |
title_sort | estrogen-related receptor γ is a novel catabolic regulator of osteoarthritis pathogenesis |
topic | Perspective |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933210/ https://www.ncbi.nlm.nih.gov/pubmed/29366446 http://dx.doi.org/10.5483/BMBRep.2018.51.4.019 |
work_keys_str_mv | AT sonyoungok estrogenrelatedreceptorgisanovelcatabolicregulatorofosteoarthritispathogenesis AT chunjangsoo estrogenrelatedreceptorgisanovelcatabolicregulatorofosteoarthritispathogenesis |