Abstract: Objective: To investigate the improving effect of ethyl ester type fish oil (FO) on cartilage degeneration in mice with posttraumatic osteoarthritis. Methods: Nine-week-old male C57BL/6J mice were used to establish an animal model of osteoporosis induced by surgical destabilization of the medial meniscus (DMM). At 7 weeks after the operation, these mice were randomly divided into four groups: sham control group, osteoporosis model, positive control, low-dose FO, and high-dose FO groups. All the animals were orally administered once daily for 60 days. After the administration period, cartilage was harvested for HE staining, toluidine blue staining and quantitative real-time polymerase chain reaction (qPCR) analysis. Results: HE and toluidine blue staining indicated that FO could significantly improve the structure of cartilage and maintain its homeostasis. qPCR results revealed that FO remarkably increased the mRNA expression of Acan and Col2α1, thereby maintaining normal chondrogenic phenotype. Meanwhile, FO significantly decreased the mRNA expression of Col10α1, Runx2, Bcl-2, Bax and caspase-3, thus inhibiting chondrocyte hypertrophy and apoptosis. Mechanistically, FO could activate autophagy through up-regulating the mRNA expression of autophagy-related genes such as LC-3B and ATG5 and suppressing the mRNA expression of mTOR. Conclusion: FO can inhibit cartilage degeneration through activating chondrocyte autophagy in mice with osteoarthritis.

Key words: ethyl ester type fish oil, osteoarthritis, cartilage degeneration, hypertrophy, apoptosis, autophagy