Bone loss in an inflammatory model of osteoporosis – a role for the p2x7 receptor?

Abstract

Bone loss and osteoporosis seen in chronic inflammatory and autoimmune diseases are a major clinical problem. Inflammatory Model of Osteoporosis (IMO; Springer protocols) is the first animal model of generalized osteoporosis resulting from inflammation. IMO resembles chronic inflammatory bone loss and is believed to be caused by overproduction of cytokines, nitric oxide, prostaglandins and inhibition of bone formation.The P2X7 receptor, an ATP-gated ionchannel receptor, is expressed in many cells including immune and bone cells. The P2X7-receptor has a regulatory role in bone formation and resorption. P2X7 has also been implicated in immune function with ATP being the natural ligand. ATP is now seen as a novel inflammatory mediator. In addition, the P2X7-receptor knock-out (KO) mice have shown an attenuated immune response in arthritis models as well as a unique bone phenotype with trabecular bone resorption affected. Aim: To investigate the role of the P2X7 Receptor in IMO. Method: One hundred and fifty 14-week-old male mice went through the IMO protocol (75 WT and 75 KO). Fifteen mice were sacrificed at baseline, 30 mice injected with silica (talc) were sacrificed at 10 and 20 days, 15 mice respectively. The remaining 30 mice were injected with vehicle and sacrificed at 10 and 20 days, 15 mice respectively. The experiment was repeated with P2X7 KO mice (Pfizer). Blood was obtained by cardiopuncture. Bone mineral density was measured on a GE lunar PIXImus 2 dual-energy x-ray absorptiometer. Spleen was harvested and weighted. Spine and hind legs were harvested for further analysis; strength test and histomorphometry. SPSS v.19 was used for statistical analysis. Results: The groups were comparable at baseline and between baseline of wildtype (WT) and KO. The spleen in the Talc injected mice were of a significantly higher weight (wt: baseline mean 86 mg, vehicle inj 105 mg and talc inj 131 mg . A significant difference between the 20 days WT vehicle and talc injected were found at both spine and femur with the talc injected having a lower BMD in average (mean 0,0508 vs 0,0540; p=0,018; T-test for equality of means). No significant difference were found between the corresponding groups of KO mice in spine and femur at 20 days. Further results are expected. Conclusion: P2X7 is involved in the bone loss found in the IMO model. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None Declared. doi:10.1016/j.bone.2012.02.449 PP261 Bone mineral density and body composition in men with multiple sclerosis V. Zikan⁎, M. Tyblova, I. Raska, M. Luchavova, D. Michalska, E. Havrdova Third Department of Medicine, Department of Endocrinology and Metabolism, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic Department of Neurology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague,