An osteoarthritis subtype characterized by synovial lipid metabolism disorder and fibroblast-like synoviocyte dysfunction

作者：Xu Cao, Zhiming Cui, Zhiyu Ding, Yong Chen, Song Wu, Xinxing Wang, Junjie Huang · 发表于：Journal of Orthopaedic Translation · 年份：2022 · DOI：10.1016/j.jot.2022.02.007 · 被引用次数：49 · 研究领域：Osteoarthritis Treatment and Mechanisms、Rheumatoid Arthritis Research and Therapies、Bone Metabolism and Diseases

Background: The heterogeneity of osteoarthritis (OA) significantly limits the effectiveness of pharmacological treatments in an unselected patient population. In this context, the identification of OA subtypes is meaningful for the development of therapies that target specific types of OA pathogenesis. Methods: Expression array profiles of 70 OA and 36 control synovial samples were extracted from the GEO database. Unsupervised consensus clustering was performed based on the most variable genes to identify OA subclusters. Next, Joint samples from OA patients were obtained. We divided the OA patient into two subpopulations according to synovial ADCY7 levels. Synovium and cartilage samples from different OA subpopulations were evaluated. In addition, we established a high-fat diet (HFD)-induced rat OA model. We evaluated OA progression, lipid metabolism, synovitis and fibroblast-like synoviocytes (FLS) function in this HFD-induced OA model. Results: 70 OA patients were categorized into three distinct subclusters. We noted that one subcluster was characterized by synovial lipid metabolism disorder GO terms. We further identified the most noticeable KEGG pathway "Regulation of lipolysis in adipocytes" in this subcluster as well as the most significantly differentially expressed gene, ADCY7. We found that the ADCY7 high expressing group (32.6%) exhibited features of synovial inflammatory lipolysis epithelial-mesenchymal transition (EMT) tendency, as well as faster join space narrow...