The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Peripheral cannabinoid receptor, CB2, regulates bone mass
Open accessAbstract
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-κB 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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Osteoclast differentiation and activation
Boyle, W. J., Simonet, W. S., & Lacey, D. L. (2003) · Nature · doi:10.1038/nature01658 · Cited by 6,670
Molecular characterization of a peripheral receptor for cannabinoids
Munro, S., Thomas, K. L., & Abu-Shaar, M. (1993) · Nature · doi:10.1038/365061a0 · Cited by 5,092
Parfitt, A. M., Drezner, M. K., Glorieux, F. H., Kanis, J. A., Malluche, H., Meunier, P. J., Ott, S. M., & Recker, R. R. (1987) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650020617 · Cited by 5,016
Cannabinoid receptor localization in brain.
Herkenham, M., Lynn, A. B., Little, M. D., Johnson, M. R., Melvin, L. S., de Costa, B. R., & Rice, K. C. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.5.1932 · Cited by 2,321
Leptin Inhibits Bone Formation through a Hypothalamic Relay
Ducy, P., Amling, M., Takeda, S., Priemel, M., Schilling, A. F., Beil, F. T., Shen, J., Vinson, C., Rueger, J. M., & Karsenty, G. (2000) · Cell · doi:10.1016/s0092-8674(00)81558-5 · Cited by 2,077
Leptin-regulated endocannabinoids are involved in maintaining food intake
Di Marzo, V., Goparaju, S. K., Wang, L., Liu, J., Bátkai, S., Járai, Z., Fezza, F., Miura, G. I., Palmiter, R. D., Sugiura, T., et al. (2001) · Nature · doi:10.1038/35071088 · Cited by 1,559
Leptin regulation of bone resorption by the sympathetic nervous system and CART
Elefteriou, F., Ahn, J. D., Takeda, S., Starbuck, M., Yang, X., Liu, X., Kondo, H., Richards, W. G., Bannon, T. W., Noda, M., et al. (2005) · Nature · doi:10.1038/nature03398 · Cited by 1,311
Hildebrand, T., Laib, A., Müller, R., Dequeker, J., & Rüegsegger, P. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.7.1167 · Cited by 1,303
Riggs, B. L., Khosla, S., & Melton, L. J. (1998) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1998.13.5.763 · Cited by 1,143
Kato, M., Patel, M. S., Levasseur, R., Lobov, I., Chang, B. H.-J., Glass, D. A., Hartmann, C., Li, L., Hwang, T.-H., Brayton, C. F., et al. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200201089 · Cited by 1,086
Cited by
The Endocannabinoid System as an Emerging Target of Pharmacotherapy
Pacher, P., Bátkai, S., & Kunos, G. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.2 · Cited by 2,077
Beta-caryophyllene is a dietary cannabinoid.
Gertsch, J., Leonti, M., Raduner, S., Racz, I., Chen, J.-Z., Xie, X.-Q., Altmann, K.-H., Karsak, M., & Zimmer, A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803601105 · Cited by 906
Self-citationCannabinoid Receptors: Where They are and What They do
Mackie, K. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01671.x · Cited by 638
Is lipid signaling through cannabinoid 2 receptors part of a protective system?
Pacher, P., & Mechoulam, R. (2011) · Progress in Lipid Research · doi:10.1016/j.plipres.2011.01.001 · Cited by 414
Self-citationLigands that target cannabinoid receptors in the brain: from THC to anandamide and beyond
Pertwee, R. G. (2008) · Addiction Biology · doi:10.1111/j.1369-1600.2008.00108.x · Cited by 314
Metadata
- 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.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2006-01-09
- Volume
- 103
- Issue
- 3
- Pages
- 696-701
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1990210398
- Cited by
- 536
- References
- 49
- FWCI
- 14.73
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Peripheral cannabinoid receptor, CB2, regulates bone mass. https://app.cochat.ai/papers/10.1073/pnas.0504187103
- The paper
- 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. (2006). Peripheral cannabinoid receptor, CB2, regulates bone mass. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0504187103
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
