QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: mol.106.026435v1 70/3/786    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tam, J. Articles by Bab, I. Search for Related Content PubMed PubMed Citation Articles by Tam, J. Articles by Bab, I.

Accelerated Communication

Involvement of Neuronal Cannabinoid Receptor CB1 in Regulation of Bone Mass and Bone Remodeling

Bone Laboratory (J.T., O.O., Y.G., I.B.), Department of Medicinal Chemistry and Natural Products (R.M.) and Department of Pharmacology (E.S.), the Hebrew University of Jerusalem, Jerusalem, Israel; David R. Bloom Centre for Pharmacy, The Hebrew University School of Pharmacy, Jerusalem, Israel (E.S., R.M.); Department of Behavioral Sciences, College of Judea and Samaria, Ariel, Israel (E.F.); Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium (C.L.); Institute for Biomedical Engineering, Swiss Federal Institute of Technology and University of Zürich, Zürich, Switzerland (R.M.); Laboratory of Molecular Neurobiology, Department of Psychiatry, University of Bonn, Bonn, Germany (A.Z.); and Departments of Anesthesiology and Physiology & Biophysics, University of Washington, Seattle, Washington (K.M.)

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 (CD1^CB1-/- mice). By contrast, our preliminary studies in cb1^-/- mice, backcrossed to C57BL/6J mice (C57^CB1-/- mice), revealed low bone mass (LBM). We therefore analyzed CB1 expression in bone and compared the skeletons of sexually mature C57^CB1-/- and CD1^CB1-/- 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 C57^CB1-/- mice exhibit decreased bone formation rate and increased osteoclast number. The skeletal phenotype of the CD1^CB1-/- mice shows a gender disparity. Female mice have normal trabecular bone with a slight cortical expansion, whereas male CD1^CB1-/- 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 C57^CB1-/- 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 C57^CB1-/- and CD1^CB1-/- 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.

Address correspondence to: Prof. Itai Bab, Bone Laboratory, the Hebrew University of Jerusalem, PO Box 12272, Jerusalem 91120, Israel. E-mail: babi{at}cc.huji.ac.il

This article has been cited by other articles:

				F. Montecucco, F. Burger, F. Mach, and S. Steffens CB2 cannabinoid receptor agonist JWH-015 modulates human monocyte migration through defined intracellular signaling pathways Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1145 - H1155. [Abstract] [Full Text] [PDF]

				J. Tam, V. Trembovler, V. Di Marzo, S. Petrosino, G. Leo, A. Alexandrovich, E. Regev, N. Casap, A. Shteyer, C. Ledent, et al. The cannabinoid CB1 receptor regulates bone formation by modulating adrenergic signaling FASEB J, January 1, 2008; 22(1): 285 - 294. [Abstract] [Full Text] [PDF]