Sparstolonin B suppresses free fatty acid palmitate‐induced chondrocyte inflammation and mitigates post‐traumatic arthritis in obese mice |
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Authors: | Haiwei Ma Chenglong Xie Gaolu He Zhengtai Chen Hongwei Lu Hongqiang Wu Hancheng Cai Zihan Dai Baolong Li Cong Xu Enxing Xue |
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Affiliation: | 1. Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou China ; 2. Department of Clinical Medicine, Second Clinical Medical College, Wenzhou Medical University, Wenzhou China |
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Abstract: | Abnormal lipid metabolism, such as systemic increased free fatty acid, results in overproduction of pro‐inflammatory enzymes and cytokines, which is crucial in the development of obesity‐related osteoarthritis (OA). However, there are only a few drugs that target the lipotoxicity of OA. Recent researches have documented that the traditional Chinese medicine, Sparstolonin B (Ssn B), exerted anti‐inflammatory effects in various diseases, but not yet in OA. On the basis of this evidence, our works purposed to evaluate the effect of Ssn B on free fatty acid (FFA) palmitate (PA)‐stimulated human osteoarthritic chondrocytes and obesity‐associated mouse OA model. We found that Ssn B suppressed PA‐triggered inflammatory response and extracellular matrix catabolism in a concentration‐dependent approach. In vivo, Ssn B treatment inhibited cartilage degeneration and subchondral bone calcification caused by joint mechanical imbalance and alleviated metabolic inflammation in obesity. Mechanistically, co‐immunoprecipitine and molecular docking analysis showed that the formation of tolllike receptor 4 (TLR4)/myeloid differentiation protein‐2 (MD‐2) complex caused by PA was blocked by Ssn B. Subsequently, it leads to inactivation of PA‐caused myeloid differentiation factor 88 (MyD88)‐dependent nuclear factor‐kappaB (NF‐κB) cascade. Together, these findings demonstrated that Ssn B is a potential treatment agent for joint degenerative diseases in obese individuals. |
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Keywords: | free fatty acid, inflammation, NF‐ κ B, osteoarthritis, sparstolonin B, toll‐ like receptor 4 |
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