CBD research - Peripheral cannabinoid receptor, CB2, regulates bone mass.

2017: Peripheral cannabinoid receptor, CB2, regulates bone mass.

These results demonstrate that the endocannabinoid system is essential for the maintenance of normal bone mass by osteoblastic and osteoclastic CB2 signaling. Hence, CB2 offers a molecular target for the diagnosis and treatment of osteoporosis, the most prevalent degenerative disease in developed countries.

Authors:

Ofek O, Karsak M, Leclerc N, Fogel M, Frenkel B, Wright K, Tam J, Attar-Namdar M, Kram V, Shohami E, Mechoulam R, Zimmer A, Bab I.

Abstract:

The endogenous cannabinoids bind to and activate two G protein-coupled

receptors, the predominantly central cannabinoid receptor type 1 (CB1)
and peripheral cannabinoid receptor type 2 (CB2). Whereas CB1 mediates
the cannabinoid psychotropic, analgesic, and orectic effects, CB2 has
been implicated recently in the regulation of liver fibrosis and
atherosclerosis. Here we show that CB2-deficient mice
have a markedly accelerated age-related trabecular bone loss and
cortical expansion, although cortical thickness remains unaltered. These
changes are reminiscent of human osteoporosis and may result from
differential regulation of trabecular and cortical bone remodeling. The
CB2(-/-) phenotype is also characterized by increased activity of
trabecular osteoblasts (bone-forming cells), increased osteoclast (the
bone-resorbing cell) number, and a markedly decreased number of
diaphyseal osteoblast precursors. CB2 is expressed in osteoblasts,
osteocytes, and osteoclasts. A CB2-specific agonist that does not have
any psychotropic effects enhances endocortical osteoblast number and
activity and restrains trabecular osteoclastogenesis, apparently by
inhibiting proliferation of osteoclast precursors and receptor activator
of NF-kappaB ligand expression in bone marrow-derived
osteoblasts/stromal cells. The same agonist attenuates
ovariectomy-induced bone loss and markedly stimulates cortical thickness
through the respective suppression of osteoclast number and stimulation
of endocortical bone formation. These results demonstrate that the
endocannabinoid system is essential for the maintenance of normal bone
mass by osteoblastic and osteoclastic CB2 signaling. Hence, CB2 offers a
molecular target for the diagnosis and treatment of osteoporosis, the
most prevalent degenerative disease in developed countries.

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