| First Author | Son YO | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Issue | 1 | Pages | 2133 |
| PubMed ID | 29247173 | Mgi Jnum | J:255229 |
| Mgi Id | MGI:6112436 | Doi | 10.1038/s41467-017-01868-8 |
| Citation | Son YO, et al. (2017) Estrogen-related receptor gamma causes osteoarthritis by upregulating extracellular matrix-degrading enzymes. Nat Commun 8(1):2133 |
| abstractText | The estrogen-related receptor (ERR) family of orphan nuclear receptor is composed of ERRalpha, ERRbeta, and ERRgamma, which are known to regulate various isoform-specific functions under normal and pathophysiological conditions. Here, we investigate the involvement of ERRs in the pathogenesis of osteoarthritis (OA) in mice. Among ERR family members, ERRgamma is markedly upregulated in cartilage from human OA patients and various mouse models of OA. Adenovirus-mediated overexpression of ERRgamma in mouse knee joint or transgenic expression of ERRgamma in cartilage leads to OA. ERRgamma overexpression in chondrocytes directly upregulates matrix metalloproteinase (MMP)-3 and MMP13, which are known to play crucial roles in cartilage destruction in OA. In contrast, genetic ablation of Esrrg or shRNA-mediated downregulation of Esrrg in joint tissues abrogates experimental OA in mice. Our results collectively indicate that ERRgamma is a novel catabolic regulator of OA pathogenesis. |
