The Anabolic Role of Cannabinoid Receptor in Bone

Endocannabinoids and their G protein‐coupled cannabinoid receptors 1 (CB1) and 2 (CB2) are present in the skeleton. CB2 is expressed in osteoblast (OB), though CB1 is debatable. We have begun a characterization of the skeletal phenotype in CB1/CB2 double receptor knockout (CB1/2 dKO) mice, We also utilized specific CB1&2 receptor antagonists to examine their effects, either individually or in combination, on OB differentiation. We conducted micro‐CT analysis of femurs from 12 week‐old CB1/2 dKO mice demonstrating a significant reduction in cortical and trabecular bone volume and thickness, when compared to wild‐type mice. To examine the functional significance of CB1&2 receptors on OB differentiation, we established primary OB cultures utilizing newborn wild‐type calvaria. Alkaline phosphatase (ALP) activity was assessed to evaluate the effects of CB receptor antagonists on OB differentiation. Treatment with the CB1 or CB2 antagonist caused a significant, dose‐dependent inhibition of ALP activity. In cultures treated with both antagonists, the inhibition of ALP was more pronounced compared to either antagonist alone. Our results suggest that CB1 & CB2 are functional receptors during OB differentiation and in regulation of bone mass. Additional studies are warranted to evaluate intracellular signaling subsequent to ligand activation of CB1&2 in OBGrant Funding Source: NIH‐NIAMS AR048892