Idris AI, van ‘t Hof RJ, Greig IR, Ridge SA, Baker D, Ross RA, Ralston SH.
Accelerated osteoclastic bone resorption has a central role in the
pathogenesis of osteoporosis and other bone diseases. Identifying the
molecular pathways that regulate osteoclast activity provides a key to
understanding the causes of these diseases and to the development of new
treatments. Here we show that mice
with inactivation of cannabinoid type 1 (CB1) receptors have increased
bone mass and are protected from ovariectomy-induced bone loss.
Pharmacological antagonists of CB1 and CB2 receptors prevented
ovariectomy-induced bone loss in vivo and caused osteoclast inhibition
in vitro by promoting osteoclast apoptosis and inhibiting production of
several osteoclast survival factors. These studies show that the CB1
receptor has a role in the regulation of bone mass and
ovariectomy-induced bone loss and that CB1- and CB2-selective
cannabinoid receptor antagonists are a new class of osteoclast
inhibitors that may be of value in the treatment of osteoporosis and
other bone diseases.