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.
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.
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.
Taken together, our results suggest that activation α7-nAChRs is an important mechanism underlying the protective effects of nicotine.