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The retinoic acid receptor gamma (RAR\u03b3) has been indicated to be involved in many inflammation processes. However, the role and mechanism of RAR\u03b3 in cartilage destruction caused by inflammation in OA are still unknown. Here, we demonstrated that the RAR\u03b3 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-\u03b1 promoted the transcription and expression of RAR\u03b3 through activating the NF-\u03baB pathway in OA cartilage. In addition, the overexpression of RAR\u03b3 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\u03b3 could increase the level of p-I\u03baB\u03b1 and p-P65 to regulate the expression of downstream genes. RAR\u03b3 and I\u03baB\u03b1 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\u03b3 agonist) and TNF-\u03b1 accelerated the OA progression, including more severe cartilage layer destruction, larger knee joint diameter, and higher serum ALP levels, while LY2955303 (RAR\u03b3 inhibitor) showed the opposite result. RAR\u03b3 was also highly expressed in OA group and even higher in TNF-\u03b1 group. In conclusion, RAR\u03b3\/NF-\u03baB positive feedback loop was activated by TNF-\u03b1 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.<\/jats:p>","DOI":"10.1155\/2022\/1875736","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T03:50:08Z","timestamp":1667879408000},"page":"1-21","source":"Crossref","is-referenced-by-count":7,"title":["Retinoic Acid Receptor Gamma (RAR\u03b3) Promotes Cartilage Destruction through Positive Feedback Activation of NF-\u03baB Pathway in Human Osteoarthritis"],"prefix":"10.1155","volume":"2022","author":[{"given":"Yue-Wei","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China"},{"name":"Department of Orthopedics, The First Affiliated Hospital of Xiamen University (Tongan Branch), Xiamen 361000, 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