Bone Abstracts

α_2C Evidences demonstrate that sympathetic nervous system (SNS) activation causes osteopenia via β₂-adrenoceptor (β₂-AR) signaling. In a recent study, we showed that female mice with chronic sympathetic hyperactivity due to double knockout of adrenoceptors that negatively regulate norepinephrine release, α_2A-AR and α_2C-AR (α_2A/α_2C-ARKO), present an unexpected phenotype of high bone mass with decreased bone resorption and increased bone formation. Furthermore, we found that these animals are resistant to the thyrotoxicosis-induced osteopenia. These findings suggest that β₂-AR is not the single adrenoceptor involved in bone mass regulation and show that α₂-AR signaling may also mediate the SNS and thyroid hormone actions in the skeleton. To further investigate the participation of α_2-ARs and its possible interaction with thyroid hormone in the regulation of bone mass, we are evaluating the bone phenotype of α_2CAR KO mice (α_2CAR^−/−). A cohort of 30 day-old female congenic α_2CAR^−/− mice, in a C57BL6/J background, and their wild-type (WT) controls (n=8/group) were treated with a supraphysiological dose of triiodothyronine (T₃=7 μg/100 gBW per day) for 30 or 90 days. Surprisingly, a microtomography analysis showed that the trabecular bone volume (BV/TV) of the femur and of the fifth lumbar vertebra (L5) were, respectively, 15–45% lower and 31–83% higher in α_2CAR^−/− mice, when compared with WT animals (P<0.05 for all). Unlike the double knockout mice (α_2A/α_2C-ARKO), α_2CAR^−/− mice were as sensitive to the thyrotoxicosis-induced osteopenia as WT animals. These findings suggest that α_2C-AR may have a role in mediating the deleterious effects of the sympathetic activation in trabecular bone of vertebra and the opposite effects in the femur. In addition, these findings suggest that thyroid hormone does not interact with the SNS, via α_2C-AR, to regulate trabecular bone volume.