Activation of α7 nicotinic acetylcholine receptors prevents monosodium iodoacetate-induced osteoarthritis in rats.

Abstract

BACKGROUND/AIMS:

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.

CONCLUSION:

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

• Authors: Yuan Liu, Dongying Wu, Fanglong Song, Chenlei Zhu, Yujian Hui, Qingcheng Zhu, Jie Wu, Weimin Fan, Jun Hu
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 35 Issue 2 Pg. 627-38 ( 2015) ISSN: 1421-9778 [Electronic] Germany
• PMID: 25613062 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

• alpha7 Nicotinic Acetylcholine Receptor
• Nicotine
• Iodoacetic Acid

Topics

• Animals
• Cells, Cultured
• Chondrocytes (cytology)
• Iodoacetic Acid
• MAP Kinase Signaling System (drug effects)
• Male
• Nicotine (administration & dosage, pharmacology)
• Osteoarthritis (chemically induced, pathology, prevention & control)
• Phosphorylation (drug effects)
• Rats
• Rats, Sprague-Dawley
• alpha7 Nicotinic Acetylcholine Receptor (metabolism)