Resistin upregulates fatty acid oxidation in synoviocytes of metabolic syndrome-associated knee osteoarthritis via CAP1/PKA/CREB to promote inflammation and catabolism

作者：Lu Ding, Jinyi Ren, Yifan Huang, Jianzeng Zhang, Ziran Bai, Yi Leng, Jun-Wei Tian, Jing Wei, Minli Jin, Guan Wang, Xia Li, Xin Qi · 发表于：Arthritis Research & Therapy · 年份：2025 · DOI：10.1186/s13075-025-03527-6 · 被引用次数：10 · 研究领域：Adipokines, Inflammation, and Metabolic Diseases、Osteoarthritis Treatment and Mechanisms、Exercise and Physiological Responses

BACKGROUND: Metabolic Syndrome (MetS), as a syndrome characterized by low-grade inflammation and energy metabolism disorders, is considered to be an important systemic risk factor for knee osteoarthritis (KOA). Our previous study showed that the protein level of serum resistin was positively correlated with the degree of metabolic disorder in MetS-OA. However, whether Resistin promotes the progression of KOA synovitis and the underlying mechanisms remain unclear. This study mainly investigateswhether there were metabolism disorder which promote inflammatory and catabolic phenotype in fibroblast-like synoviocytes (FLS) from KOA patients with MetS (MetS-KOA-FLS), and the roles and mechanisim of resistin in MetS-KOA-FLS. METHODS: Comparative analysis of synovium and FLS from MetS-associated KOA (MetS-KOA) and non-MetS-associated KOA (nMetS-KOA) of females to detect the differences in inflammation, catabolism and glycolipid metabolism. Serum from MetS-KOA stimulated nMetS-KOA-FLS to detect the effect of MetS microenvironment on inflammation, catabolism and glycolipid metabolism of nMetS-KOA-FLS. Resistin stimulated MetS-KOA-FLS to explore the effect of resistin on inflammation and catabolism of MetS-KOA-FLS and its specific mechanism. RESULTS: Compared with nMetS-KOA-FLS, MetS-KOA-FLS expressed higher inflammatory related factors, catabolic enzymes, and showed stronger adhesive and invasive ability. Resistin was found to be an important factor in the serum and internal environmen...