Bone loss in chronic autoimmune inflammatory diseases is a major clinical problem. Inflammation-mediated osteoposis (IMO) is the first animal model of generalized osteoporosis resulting from inflammation. The P2×7 receptor, an ATP-gated ion-channel, is primarily expressed on immune and bone cells. ATP is now seen as a novel inflammatory mediator, with P2×7 as main target of the pro-inflammatory activity. The P2×7-receptor has a regulatory role in bone formation and resorption. In addition, P2×7-receptor knock-out (KO) mice have shown an attenuated immune response.
Aim: To investigate the role of the P2×7 receptor in IMO.
Method: Fourteen-week-old male mice entered 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 at each time point). The remaining 30 mice were injected with vehicle and sacrificed at 10 and 20 days, (15 mice at each time point). The experiment was repeated with P2×7 KO mice (Pfizer). Bone mineral density (BMD) was measured by PIXImus. Spleen was collected and weighted. Blood, spine and hind legs were collected for further analysis; strength test and histomorphometry. Data: mean±S.D.
Results: In WT animals, the spleen weight was higher in the Talc injected mice (WT: baseline 86±13 mg, vehicle 109±32 mg and Talc injected 131±44 mg). No difference in KO.
Spine BMD was significantly lower at 20 days compared to baseline in WT vs Talc (ANCOVA weight corrected: P=0.032). Moreover, at 20 days spine BMD was significantly lower in the Talc WT group compared to vehicle (0.046 vs 0.051 g/cm: P=0.009). In the KO animals no significant difference was found at 20 days between vehicle and Talc group (0.052 vs 0.052 g/cm) (ns).
Conclusion: P2×7 might be involved in the inflammation-mediated osteoporosis.
27 Apr - 01 May 2013
European Society of Endocrinology