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Enhancement of the synthesis of n-3 PUFAs in fat-1 transgenic mice inhibits mTORC1 signalling and delays surgically induced osteoarthritis in comparison with wild-type mice
  1. Min-jun Huang1,2,
  2. Liang Wang1,2,
  3. Da-di Jin1,2,
  4. Zhong-min Zhang1,2,
  5. Tian-yu Chen1,2,
  6. Chun-hong Jia3,
  7. Yan Wang4,
  8. Xiao-chen Zhen1,2,
  9. Bin Huang1,2,
  10. Bo Yan1,2,
  11. Yu-hui Chen1,2,
  12. Sheng-fa Li1,2,
  13. Jin-cheng Yang5,
  14. Yi-fan Dai4,
  15. Xiao-chun Bai2,3
  1. 1Department of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, PR China
  2. 2Academy of Orthopedics, Guangdong Province, Guangzhou, Guangdong, PR China
  3. 3Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, PR China
  4. 4The Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, Jiangsu, PR China
  5. 5Department of Orthopedics, Liu Hua Qiao Hospital, Guangzhou, Guangdong, PR China
  1. Correspondence to Dr Xiao-chun Bai, Department of Cell Biology, School of Basic Medical Science, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China; baixc15{at}


Background An exogenous supplement of n-3 polyunsaturated fatty acids (PUFAs) has been reported to prevent osteoarthritis (OA) through undefined mechanisms.

Objective This study investigated the effect of alterations in the composition of endogenous PUFAs on OA, and associations of PUFAs with mammalian target of rapamycin complex 1 (mTORC1) signalling, a critical autophagy pathway in fat-1 transgenic (TG) mice.

Methods fat-1 TG and wild-type mice were used to create an OA model by resecting the medial meniscus. The composition of the endogenous PUFAs in mouse tissues was analysed by gas chromatography, and the incidence of OA was evaluated by micro-computed tomography (micro-CT), scanning electron microscopy and histological methods. Additionally, primary chondrocytes were isolated and cultured. The effect of exogenous and endogenous PUFAs on mTORC1 activity and autophagy in chondrocytes was assessed.

Results The composition of endogenous PUFAs of TG mice was optimised both by increased n-3 PUFAs and decreased n-6 PUFAs, which significantly alleviated the articular cartilage destruction and osteophytosis in the OA model (p<0.01), decreased protein expression of matrix metalloproteinase-13 (MMP-13) and ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin motifs) in the articular cartilage (p<0.01) and reduced chondrocyte number and loss of cartilage extracellular matrix. Both exogenous and endogenous n-3 PUFAs downregulated mTORC1 activity and promoted autophagy in articular chondrocytes. Conversely, mTORC1 pathway activation suppressed autophagy in articular chondrocytes.

Conclusions Enhancement of the synthesis of endogenous n-3 PUFAs from n-6 PUFAs can delay the incidence of OA, probably through inhibition of mTORC1, promotion of autophagy and cell survival in cartilage chondrocytes. Future investigation into the role of the endogenous n-6/n-3 PUFAs composition in OA prevention and treatment is warranted.

  • Chondrocytes
  • Osteoarthritis
  • Inflammation
  • Cytokines

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