Weeding Out Osteoclasts

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Science  03 Jun 2005:
Vol. 308, Issue 5727, pp. 1379
DOI: 10.1126/science.308.5727.1379b

More than half of individuals age 50 and older are at risk for osteoporosis, a disorder characterized by low bone mass. One of the principal cell types regulating skeletal growth and integrity is the osteoclast, which functions to resorb bone. Several drugs currently in clinical use for osteoporosis, such as the bisphosphonates, act by inhibiting osteoclast activity.

A surprising new molecular player in bone growth and remodeling is identified by Idris et al., who find that mutant mice deficient in cannabinoid type 1 (CB1) receptors have increased bone mass that appears to be caused by aberrant apoptosis (cell death) of osteoclasts. Moreover, mutant female mice were protected against bone loss induced by ovary removal, which is a model of postmenopausal bone loss in women, and this protective effect could be reproduced pharmacologically in wild-type mice by the administration of cannabinoid antagonists. Thus, osteoporosis joins a growing list of human disorders, including obesity and nicotine dependence, that may be treatable by drugs targeting the cannabinoid receptors, a class of proteins originally discovered as the binding sites for the major psychoactive ingredient of marijuana. — PAK

Nat. Med. 10.1038/nm1255 (2005).

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