Retinoic Acid Receptor Gamma (RARγ) Promotes Cartilage Destruction through Positive Feedback Activation of NF-κB Pathway in Human Osteoarthritis. (7th November 2022)

• Record Type: Journal Article
• Authors: Yu, Yue-Wei; Li, Si-Yang; Zhang, Lin-Jun; Wang, Qian-Liang; Liu, Zhong-Guo; Chen, Qing-Zhi; Song, Hong-Yu; Shen, Dong-Yan; Yan, Jun
• Other Names: Fioravanti Antonella Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2022(2022)
• Publication Date: 2022-11-07
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2022/1875736
• Languages: English
• ISSNs: 0962-9351

Abstract

Abstract : Osteoarthritis (OA) is a severe inflammation-related disease which leads to cartilage destruction. The retinoic acid receptor gamma (RAR γ ) has been indicated to be involved in many inflammation processes. However, the role and mechanism of RAR γ in cartilage destruction caused by inflammation in OA are still unknown. Here, we demonstrated that the RAR γ was highly expressed in chondrocytes of OA patients compared with healthy people and was positively correlated with the damage degree of cartilage in OA. Cytokine TNF- α promoted the transcription and expression of RAR γ through activating the NF- κ B pathway in OA cartilage. In addition, the overexpression of RAR γ resulted in the upregulation of matrix degradation and inflammation associated genes and downregulation of differentiation and collagen production genes in human normal chondrocyte C28/I2 cells. Mechanistically, overexpression of RAR γ could increase the level of p-I κ B α and p-P65 to regulate the expression of downstream genes. RAR γ and I κ B α also could interact with each other and had the same localization in C28/I2 cells. Moreover, the SD rats OA model induced by monosodium iodoacetate indicated that CD437 (RAR γ agonist) and TNF- α accelerated the OA progression, including more severe cartilage layer destruction, larger knee joint diameter, and higher serum ALP levels, while LY2955303 (RAR γ inhibitor) showed the opposite result. RAR γ was also highly expressed in OA group and even higher in TNF- α group. In conclusion, RAR γ /NF- κ B positive feedback loop was activated by TNF- α in chondrocyte to promote cartilage destruction. Our data not only propose a novel and precise molecular mechanism for OA disease but also provide a prospective strategy for the treatment.