title: Resveratrol, a natural antioxidant, protects monosodium iodoacetate-induced osteoarthritic pain in rats.
abstract: BACKGROUND
  Osteoarthritis (OA) is a chronic progressive joint disease characterized by advanced joint pain, subchondral bone sclerosis and articular cartilage degeneration. Resveratrol has been shown to have anti-inflammatory, cardioprotective and antioxidant properties and to inhibit platelet aggregation and coagulation. However, the effects of resveratrol on OA have not been examined. In this study, we investigate the protective effects of resveratrol on monosodium iodoacetate (MIA)-induced OA through inhibition of cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) signaling pathway in a rat model.
  
  
  METHODS
  A single intra-articular injection of MIA was injected into rats for the induction of OA. The mechanical, heat and cold hyperalgesia were measured at days 0, 7 and 14. The serum and synovial fluid levels of IL-1β, IL-10 and TNF-α and osteocalcin were measured by enzyme-linked immunosorbent assay. The mRNA and protein expressions of IL-1β, IL-10, TNF-α, Il-6, MMP-13 and COX-2 and iNOS were determined by RT-PCR and western blot, respectively. Osteoarthritic lesion in the knee joint was evaluated by histological analysis.
  
  
  RESULTS
  MIA-injected rats treated with resveratrol at a dose of either 5 or 10mg/kg body weight were significantly reduced hyperalgesia of mechanical, heat and cold and increased the vertical and horizontal movements. Subsequently, MIA-injected rats increased serum and synovial fluid levels of IL-1β, IL-10, IL-6, TNF-α, MMP-13 and osteoclastic activity marker, osteocalcin and its articular cartilage mRNA and protein expressions. Further, MIA-injected rats increased COX-2 and iNOS mRNA and protein expressions were decreased by resveratrol. The protective effect of resveratrol was comparable to a reference drug, etoricoxib. The cartilage damage induced by MIA were attenuated by resveratrol.
  
  
  CONCLUSIONS
  Taken together, resveratrol has the potential to improve MIA-induced cartilage damage by inhibiting the levels and expressions of inflammatory mediators suggesting that resveratrol may be a potential therapeutic agent for OA.
authors.affiliation: Department of Bone and Hand Microsurgery, Shandong Wendeng Orthopedic and Traumatic Hospital, Shandong, China.
authors.forename: Zhu-Min
authors.initials: ZM
authors.lastname: Wang
authors.affiliation: Department of Microsurgery, The First Affiliated Hospital of Henan University of Science and Technology, LuoYang, China.
authors.forename: Yong-Cai
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Osteology, Zhengzhou Orthopaedics Hospital, No. 58 the Longhai Road, Two seven District, Zhengzhou City, Henan, 450000, China. Electronic address: wangdapeng2491@hotmail.com.
authors.forename: Da-Peng
authors.initials: DP
authors.lastname: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000235:genetics; D005121:Extremities / Q000473:pathology; D006930:Hyperalgesia / Q000097:blood / Q000150:complications / Q000188:drug therapy; D007461:Iodoacetates; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010003:Osteoarthritis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control*; D010146:Pain / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D013582:Synovial Fluid / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016207:Cytokines; D007461:Iodoacetates; D012333:RNA, Messenger; D013267:Stilbenes; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D000077185:Resveratrol
keywords: Cytokines and inflammation; Monosodium iodoacetate; Osteoarthritis; Resveratrol