title: Captopril, an angiotensin-converting enzyme inhibitor, possesses chondroprotective efficacy in a rat model of osteoarthritis through suppression local renin-angiotensin system.
abstract: OBJECTIVE
  A local tissue-specific renin-angiotensin system (local RAS) has emerged as a regulator of cartilage development and homeostasis. However, no report has described the chondroprotective efficacy of RAS inhibitor. Therefore, we studied the pharmacological function of captopril on hypertrophic differentiation of chondrocytes, cartilaginous degeneration and RAS components expression in a rat model of osteoarthritis (OA).
  
  
  METHODS
  OA was surgically induced in the right knee of male rats. Animal groups included age matched sham control (sham group), OA placebo (OA group), and OA treated with captopril (CAP group). Eight weeks after the induction of OA, the tibias were isolated and the sagittal sections were stained with Safranin O and Masson-Trichrome. The mRNA and protein expression of RAS components were measured by qRT-PCR and western blotting respectively.
  
  
  RESULTS
  The thickness of articular cartilage was reduced in the proximal tibia of the OA group, and decreased thickness of articular cartilage of the OA mice was effectively reversed by captopril treatment. Histological analyses revealed remarkable chondrocytes abnormality in OA rats, which were characterized by a marked expansion of hypertrophic zone and inhibition of proliferative zone of chondrocytes in the epiphyseal growth plate of tibia. However, captopril-treated could reverse chondrocytes abnormality in OA rats. Furthermore, the mRNA and protein expression of RAS components, renin, ACE, Ang II AT1R were upregulated in the proximal tibia of OA rats, however, the AT2R expression was suppressed. Intriguingly, captopril-treated could inhibit the activation of RAS in OA rats.
  
  
  CONCLUSIONS
  The present study demonstrated that captopril could attenuate OA-induced osteoarticular injury, at least partially, through suppression local RAS.
authors.affiliation: Department of Orthopaedics, Shanghai Third People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Orthopaedics, Shanghai Third People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Orthopaedics, Shanghai Third People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Lu
keywords: Osteoarthritis; captopril; chondrocytes; renin-angiotensin system