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Endocannabinoids and the Regulation of Bone Metabolism
Author(s) -
Bab I.,
Ofek O.,
Tam J.,
Rehnelt J.,
Zimmer A.
Publication year - 2008
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.2008.01675.x
Subject(s) - endocrinology , medicine , endocannabinoid system , bone remodeling , bone resorption , chemistry , cannabinoid receptor , 2 arachidonoylglycerol , osteoporosis , bone cell , receptor , cortical bone , microbiology and biotechnology , agonist , biology , anatomy
In mammals, including humans, bone metabolism is manifested as an ongoing modelling/remodelling process whereby the bone mineralised matrix is being continuously renewed. Recently, the main components of the endocannabinoid system have been reported in the skeleton. Osteoblasts, the bone forming cells, and other cells of the osteoblastic lineage, as well as osteoclasts, the bone resorbing cells, and their precursors, synthesise the endocannabinoids anandamide and 2‐arachidonoylglycerol (2‐AG). CB 1 cannabinoid receptors are present in sympathetic nerve terminals in close proximity to osteoblasts. Activation of these CB 1 receptors by elevated bone 2‐AG levels communicates brain‐to‐bone signals as exemplified by traumatic brain injury‐induced stimulation of bone formation. In this process, the retrograde CB 1 signalling inhibits noradernaline release and alleviates the tonic sympathetic restrain of bone formation. CB 2 receptors are expressed by osteoblasts and osteoclasts. Their activation stimulates bone formation and suppresses bone resorption. CB 2 ‐deficient mice display a markedly accelerated age‐related bone loss. Ovariectomy‐induced bone loss can be both prevented and rescued by a CB 2 specific agonist. Hence, synthetic CB 2 ligands, which are stable and orally available, provide a basis for developing novel anti‐osteoporotic therapies, free of psychotropic effects. The CNR2 gene (encoding CB 2 ) in women is associated with low bone mineral density, offering an assay for identifying females at risk of developing osteoporosis.