Drug Design, Development and Therapy (Jul 2020)
Cordycepin Alleviates Anterior Cruciate Ligament Transection (ACLT)-Induced Knee Osteoarthritis Through Regulating TGF-β Activity and Autophagy
Abstract
Xiao-Mei Tao,1– 3,* Peng-Fei Liu,1,* Hong-Yan Gu,1– 3 Dong-Bo Lian,1 Lei Gao,1 Wei-Wei Tao,4 Dan Yan,1– 3 Bin Zhao5 1Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, People’s Republic of China; 2Beijing Key Laboratory of Bio-Characteristic Profiling for Evaluation of Clinical Rational Drug Use, Beijing Municipal Science and Technology Commission, Beijing 100038, People’s Republic of China; 3International Cooperation & Joint Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use, Beijing Municipal Science & Technology Commission, Beijing 100038, People’s Republic of China; 4College of Nursing, Dalian Medical University, Dalian 116044, People’s Republic of China; 5Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei-Wei Tao; Bin Zhao Tel +86 13610862836; +86 13811825981Email [email protected]; [email protected]: Osteoarthritis is the most prevalent articular disease in the elderly. We aimed to explore the role of cordycepin (COR) in the progression and development of osteoarthritis and its correlation with TGF-β activity and autophagy.Methods: Sprague Dawley rats were induced by anterior cruciate ligament transection (ACLT) to establish knee osteoarthritis model. To investigate the role of COR in knee osteoarthritis, rats were injected with 5, 10, and 20 mg/kg of COR before joint surgery. After surgery, paw withdrawal mechanical threshold (PWMT) was performed. HE staining and Alcian blue staining were carried out to detect cartilage damage. ELISA was used to detect the level of TGFβ in the serum. Protein expression was analyzed by Western blotting.Results: In this study, we found that the PWMT of rats with osteoarthritis induced by ACLT was decreased significantly, accompanied by obvious histological and cartilage damage. After different doses of COR treatment, the PWMT of osteoarthritis rats induced by ACLT was increased in a dose-dependent manner. In addition, compared with the control group, COR treatment also reversed the effect of ACLT on cartilage injury in rats. Furthermore, the level of TGF-β in serum of ACLT rats was increased significantly, which may be related to the overexpression of TGF-β R1. However, the increase of serum TGF-β level in ACLT rats was reversed by COR treatment in a dose-dependent manner. It is worth noting that TGF-β overexpression reduced the proportion of autophagy-related protein LC3-II/I, thus inhibiting autophagy. In order to further confirm the effect of TGF-β on autophagy, TGF-β was overexpressed or the autophagy inhibitor 3-MA was applied. The results showed that TGF-β overexpression and 3-MA treatment reversed the effect of COR on autophagy.Conclusion: In summary, our findings declared that COR alleviated ACLT-induced osteoarthritis pain and cartilage damage by inhibiting TGF-β activity and inducing autophagy in rat model with knee osteoarthritis.Keywords: cordycepin, anterior cruciate ligament transection, osteoarthritis, TGF-β, autophagy, in vivo
