2. Academic Validation
  3. n-3 polyunsaturated fatty acids alleviate the progression of obesity-related osteoarthritis and protect cartilage through inhibiting the HMGB1-RAGE/TLR4 signaling pathway

n-3 polyunsaturated fatty acids alleviate the progression of obesity-related osteoarthritis and protect cartilage through inhibiting the HMGB1-RAGE/TLR4 signaling pathway

  • Int Immunopharmacol. 2024 Jan 12:128:111498. doi: 10.1016/j.intimp.2024.111498.
Tao Xiong 1,  Shiqi Huang 2,  Xinjuan Wang 3,  Yu Shi 4,  Jianyi He 5,  Ye Yuan 6,  Ruiqi Wang 7,  Hailun Gu 8,  Li Liu 9
Affiliations

Affiliations

  • 1 Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning 110122, PR China; Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, 110122, PR China. Electronic address: 2698671892@qq.com.
  • 2 Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning 110122, PR China; Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, 110122, PR China. Electronic address: 1102435641@qq.com.
  • 3 Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning 110122, PR China; Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, 110122, PR China. Electronic address: 824731815@qq.com.
  • 4 Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning 110122, PR China; Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, 110122, PR China. Electronic address: 736748540@qq.com.
  • 5 Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning 110122, PR China; Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, 110122, PR China. Electronic address: a1002994179@163.com.
  • 6 Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning 110122, PR China; Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, 110122, PR China. Electronic address: 1090050675@qq.com.
  • 7 Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning 110122, PR China; Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, 110122, PR China. Electronic address: 1132160217@qq.com.
  • 8 Department of Orthopedics, Shengjing Hospital, China Medical University, 110004, PR China. Electronic address: guhailun_@163.com.
  • 9 Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning 110122, PR China; Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, 110122, PR China. Electronic address: lliu@cmu.edu.cn.
PMID: 38218011 DOI: 10.1016/j.intimp.2024.111498
Abstract

Osteoarthritis (OA) is a common joint degenerative disease. There is currently no cure for OA. Dietary fatty acids have potential value in the prevention and treatment of OA. n-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory effects, but their anti-OA mechanism remains unclear. High-mobility group box 1 (HMGB1) promotes inflammation and participates the pathogenesis of OA. The purpose of this study was to investigate the protective effect of n-3 PUFAs on cartilage and whether n-3 PUFAs could exert an anti-OA effect through inhibiting HMGB1-RAGE/TLR4 signaling pathway. We established an obesity-related post-traumatic OA mice model and an in vitro study was conducted to explore the regulatory mechanism of n-3 PUFAs on HMGB1 and its signal pathway against OA. We found that diet rich in n-3 PUFAs alleviated OA-like lesions of articular cartilage with the decrease of HMGB1-RAGE/TLR4 signaling protein in mice. In SW1353 cells, DHA significantly reduced the expression of HMGB1-RAGE/TLR4 signaling protein which was up-regulated by IL-1β stimulation. HMGB1 overexpression reversed the inhibitory effect of DHA on HMGB1-RAGE/TLR4 signaling pathway. The activation of SIRT1 may participate the inhibitory effect of DHA on HMGB1-RAGE/TLR4 signaling pathway. In conclusion, n-3 PUFAs could attenuate the progression of obesity-related OA and exert protective effect on cartilage by inhibiting HMGB1-RAGE/TLR4 signaling pathway, which may be associated with the activation of SIRT1. Dietary n-3 PUFAs supplements can be considered as a potential therapeutic substance for OA.

Keywords

High-mobility group box 1; Obesity; Osteoarthritis; Receptor for advanced glycation end products; Toll-like receptor 4; n-3 Polyunsaturated fatty acids.

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