Peripheral cannabinoid receptor, CB2, regulates bone mass. Export

@article{citeulike:6021368, 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.}, author = {Ofek, Orr and Karsak, Meliha and Leclerc, Nathalie and Fogel, Meirav and Frenkel, Baruch and Wright, Karen and Tam, Joseph and Attar-Namdar, Malka and Kram, Vardit and Shohami, Esther and Mechoulam, Raphael and Zimmer, Andreas and Bab, Itai}, citeulike-article-id = {6021368}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0504187103}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16407142}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16407142}, day = {17}, doi = {10.1073/pnas.0504187103}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {bone-remodeling, bone\_histomorphometry\_fig, calvaria, cb-recep, endocannabinoid, ob\_oc, pth, rankl}, month = {January}, number = {3}, pages = {696--701}, posted-at = {2009-10-28 16:54:47}, priority = {2}, title = {Peripheral cannabinoid receptor, CB2, regulates bone mass.}, url = {http://dx.doi.org/10.1073/pnas.0504187103}, volume = {103}, year = {2006} }

TY - JOUR ID - citeulike:6021368 L3 - citeulike-article-id:6021368 N2 - 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. IS - 3 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 0027-8424 EP - 701 TI - Peripheral cannabinoid receptor, CB2, regulates bone mass. VL - 103 SP - 696 KW - bone-remodeling KW - bone_histomorphometry_fig KW - calvaria KW - cb-recep KW - endocannabinoid KW - ob_oc KW - pth KW - rankl AU - Ofek, Orr AU - Karsak, Meliha AU - Leclerc, Nathalie AU - Fogel, Meirav AU - Frenkel, Baruch AU - Wright, Karen AU - Tam, Joseph AU - Attar-Namdar, Malka AU - Kram, Vardit AU - Shohami, Esther AU - Mechoulam, Raphael AU - Zimmer, Andreas AU - Bab, Itai PY - 2006/01/17/ UR - http://dx.doi.org/10.1073/pnas.0504187103 ER -