Cordycepin Alleviates Anterior Cruciate Ligament Transection (ACLT)-Induced Knee Osteoarthritis Through Regulating TGF-β Activity and Autophagy

Drug Des Devel Ther. 2020 Jul 17:14:2809-2817. doi: 10.2147/DDDT.S251893. eCollection 2020.

Abstract

Introduction: 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: TGF-β; anterior cruciate ligament transection; autophagy; cordycepin; in vivo; osteoarthritis.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Anterior Cruciate Ligament*
  • Autophagy / drug effects
  • Deoxyadenosines / administration & dosage
  • Deoxyadenosines / pharmacology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / pharmacology*
  • Injections, Intravenous
  • Male
  • Medicine, Chinese Traditional
  • Osteoarthritis, Knee / drug therapy*
  • Osteoarthritis, Knee / metabolism
  • Osteoarthritis, Knee / surgery*
  • Rats
  • Rats, Sprague-Dawley
  • Transforming Growth Factor beta / antagonists & inhibitors*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism

Substances

  • Deoxyadenosines
  • Drugs, Chinese Herbal
  • Transforming Growth Factor beta
  • cordycepin

Grants and funding

This work was supported by Youth Fund of Beijing Shijitan Hospital (2016-C11), the National Great New Drugs Development Project of China (2017ZX09301-040), Liaoning Natural Science Foundation, China (20180550642), The Educational Commission of Liaoning Province, China (LQ2017044), Open Research Funding of Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use (2020), and Enhancement Funding of Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use(BZ0439).