RT Journal Article
SR Electronic
T1 Involvement of Neuronal Cannabinoid Receptor CB1 in Regulation of Bone Mass and Bone Remodeling
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 786
OP 792
DO 10.1124/mol.106.026435
VO 70
IS 3
A1 Joseph Tam
A1 Orr Ofek
A1 Ester Fride
A1 Catherine Ledent
A1 Yankel Gabet
A1 Ralph Müller
A1 Andreas Zimmer
A1 Ken Mackie
A1 Raphael Mechoulam
A1 Esther Shohami
A1 Itai Bab
YR 2006
UL http://molpharm.aspetjournals.org/content/70/3/786.abstract
AB The CB1 cannabinoid receptor has been implicated in the regulation of bone remodeling and bone mass. A high bone mass (HBM) phenotype was reported in CB1-null mice generated on a CD1 background (CD1CB1-/- mice). By contrast, our preliminary studies in cb1-/- mice, backcrossed to C57BL/6J mice (C57CB1-/- mice), revealed low bone mass (LBM). We therefore analyzed CB1 expression in bone and compared the skeletons of sexually mature C57CB1-/- and CD1CB1-/- mice in the same experimental setting. CB1 mRNA is weakly expressed in osteoclasts and immunoreactive CB1 is present in sympathetic neurons, close to osteoblasts. In addition to their LBM, male and female C57CB1-/- mice exhibit decreased bone formation rate and increased osteoclast number. The skeletal phenotype of the CD1CB1-/- mice shows a gender disparity. Female mice have normal trabecular bone with a slight cortical expansion, whereas male CD1CB1-/- animals display an HBM phenotype. We were surprised to find that bone formation and resorption are within normal limits. These findings, at least the consistent set of data obtained in the C57CB1-/- line, suggest an important role for CB1 signaling in the regulation of bone remodeling and bone mass. Because sympathetic CB1 signaling inhibits norepinephrine (NE) release in peripheral tissues, part of the endocannabinoid activity in bone may be attributed to the regulation of NE release from sympathetic nerve fibers. Several phenotypic discrepancies have been reported between C57CB1-/- and CD1CB1-/- mice that could result from genetic differences between the background strains. Unraveling these differences can provide useful information on the physiologic functional milieu of CB1 in bone. The American Society for Pharmacology and Experimental Therapeutics