title: Activation of α7 nicotinic acetylcholine receptors prevents monosodium iodoacetate-induced osteoarthritis in rats.
abstract: OBJECTIVE
  Although some evidence suggests that the prevalence of osteoarthritis (OA) is lower in smokers compared to nonsmokers, the mechanisms of nicotine-induced protection remain unclear. Stimulation of the α7 nicotinic acetylcholine receptor (α7-nAChR) appears to be a critical mechanism underlying the anti-inflammatory potential of cholinergic agonists in immune cells. The inhibition of secreted inflammatory molecules and the subsequent inflammatory processes have been proposed as a novel strategy for the treatment of OA. The objective of the present study was to determine whether nicotine-induced protection in a monosodium iodoacetate (MIA) rat model of OA occurs via α7-nAChR-mediated inhibition of chondrocytes.
  
  
  METHODS
  Both in vivo (MIA) and in vitro (MIA; Interleukin-1β, IL-1β) models of OA were used to investigate the roles and the possible mechanisms whereby α7-nAChRs protect against knee joint degradation. Multiple experimental approaches, including macroscopic, histological analysis, chondrocyte cell cultures, confocal microscopy, and western blotting, were employed to elucidate the mechanisms of α7-nAChR-mediated protection.
  
  
  RESULTS
  Systemic administration of nicotine alleviated MIA-induced joint degradation. The protective effects of nicotine were abolished by administration of the α7-nAChR-selective antagonist methyllycaconitine (MLA). In primary cultured rat chondrocytes, pretreatment with nicotine suppressed both p38, extracellular regulated kinase (Erk) 1/2 and c-Jun-N-terminal kinase (JNK) mitogen-activated protein kinases (MAPK) phosphorylation and phosphorylated nuclear factor-kappa B (NF-κB) p65 activation induced by MIA- or IL-1β, and these effects were also reversed by MLA.
  
  
  CONCLUSIONS
  Taken together, our results suggest that activation α7-nAChRs is an important mechanism underlying the protective effects of nicotine.
authors.affiliation: Department of Orthopedics, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Dongying
authors.initials: D
authors.lastname: Wu
authors.forename: Fanglong
authors.initials: F
authors.lastname: Song
authors.forename: Chenlei
authors.initials: C
authors.lastname: Zhu
authors.forename: Yujian
authors.initials: Y
authors.lastname: Hui
authors.forename: Qingcheng
authors.initials: Q
authors.lastname: Zhu
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Weimin
authors.initials: W
authors.lastname: Fan
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology*; D019807:Iodoacetic Acid; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D009538:Nicotine / Q000008:administration & dosage* / Q000494:pharmacology; D010003:Osteoarthritis / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
chemical_list: D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; D019807:Iodoacetic Acid