Putative model for the regulation of bone resorption and formation by CB2 in the trabecular and cortical bone compartments.
CB2 directly inhibits osteoclastogenesis and bone resorption. In the trabecular bone, direct activation of CB2 in osteoblasts is antagonized by the inhibitory action of NO release induced by CB2 in non-skeletal cells, resulting in an overall attenuation of trabecular bone formation. CB2–/– animals are therefore characterized by a strongly increased bone resorption and mildly increased bone formation, resulting in a net trabecular bone loss. The endosteal bone loss, resulting in medullary expansion, is likely caused by an increased bone resorption and decreased bone formation.