IB-MECA, an A3 adenosine receptor agonist prevents bone resorption in rats with adjuvant induced arthritis

CER2828
2006 Vol.24, N°4
PI 0400, PF 0406
Full Papers

Free to view
(click on article PDF icon to read the article)

PMID: 16956430 [PubMed]

Abstract

OBJECTIVES:
The anti-inflammatory effect of adenosine is partially mediated via the A3 adenosine receptor (A<inf>3</inf>AR), a Gi protein associated cell surface receptor. The highly selective A<inf>3</inf>AR agonist, IB-MECA was earlier shown to prevent the clinical and pathological manifestations of arthritis in experimental animal models of collagen and adjuvant induced arthritis (AIA). In this study we tested the effect of IB-MECA on the prevention of bone resorption in AIA rats and looked at the molecular mechanism of action.
METHODS:
Rats with AIA were treated orally twice daily with IB-MECA starting upon onset of disease and the clinical score was evaluated every other day. At study termination the foot, knee and hip region of both vehicle and IB-MECA treated animals were subjected to histomorphometric analysis. Western blot analysis was carried out on paw protein extracts.
RESULTS:
IB-MECA ameliorated the clinical manifestations of the disease and reduced pannus and fibrosis formation, attenuated cartilage and bone destruction and decreased the number of osteoclasts. In cell protein extracts derived from paw of AIA rats, A<inf>3</inf>AR was highly expressed in comparison to naïve animals. In paw extracts derived from IB-MECA treated AIA rats, down-regulation of the A<inf>3</inf>AR protein expression level was noted. PI3K, PKB/Akt, IKK, NF-κB, TNF-α and RANKL were down-regulated whereas caspase 3 was up-regulated.
CONCLUSIONS:
IB-MECA, a small highly bioavailable molecule, induces modulation of proteins which control survival and apoptosis resulting in the amelioration of the inflammatory process and the preservation of bone mass in AIA rats.