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Cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts.
J Bone Miner Res. 2015 Oct; 30(10):1905-13.JB

Abstract

Cannabinoid ligands regulate bone mass, but skeletal effects of cannabis (marijuana and hashish) have not been reported. Bone fractures are highly prevalent, involving prolonged immobilization and discomfort. Here we report that the major non-psychoactive cannabis constituent, cannabidiol (CBD), enhances the biomechanical properties of healing rat mid-femoral fractures. The maximal load and work-to-failure, but not the stiffness, of femurs from rats given a mixture of CBD and Δ(9) -tetrahydrocannabinol (THC) for 8 weeks were markedly increased by CBD. This effect is not shared by THC (the psychoactive component of cannabis), but THC potentiates the CBD stimulated work-to-failure at 6 weeks postfracture followed by attenuation of the CBD effect at 8 weeks. Using micro-computed tomography (μCT), the fracture callus size was transiently reduced by either CBD or THC 4 weeks after fracture but reached control level after 6 and 8 weeks. The callus material density was unaffected by CBD and/or THC. By contrast, CBD stimulated mRNA expression of Plod1 in primary osteoblast cultures, encoding an enzyme that catalyzes lysine hydroxylation, which is in turn involved in collagen crosslinking and stabilization. Using Fourier transform infrared (FTIR) spectroscopy we confirmed the increase in collagen crosslink ratio by CBD, which is likely to contribute to the improved biomechanical properties of the fracture callus. Taken together, these data show that CBD leads to improvement in fracture healing and demonstrate the critical mechanical role of collagen crosslinking enzymes.

Authors+Show Affiliations

Bone Laboratory, Hebrew University of Jerusalem, Jerusalem, Israel.Bone Laboratory, Hebrew University of Jerusalem, Jerusalem, Israel.Bone Laboratory, Hebrew University of Jerusalem, Jerusalem, Israel.Bone Laboratory, Hebrew University of Jerusalem, Jerusalem, Israel. Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.Institute for Drug Research, Hebrew University of Jerusalem, Jerusalem, Israel.Institute for Biomechanics, ETH Zürich, Zürich, Switzerland.Institute for Biomechanics, ETH Zürich, Zürich, Switzerland.Institute for Biomechanics, ETH Zürich, Zürich, Switzerland.Bone Laboratory, Hebrew University of Jerusalem, Jerusalem, Israel.Bone Laboratory, Hebrew University of Jerusalem, Jerusalem, Israel.Department of Oral Medicine, Hadassah-Hebrew University Faculty of Dental Medicine, Jerusalem, Israel.Department of Biomedical Engineering, Lund University, Lund, Sweden. Department of Orthopedics, Lund University, Lund, Sweden.Department of Biomedical Engineering, Lund University, Lund, Sweden. Department of Orthopedics, Lund University, Lund, Sweden.Institute for Drug Research, Hebrew University of Jerusalem, Jerusalem, Israel.Institute for Biomechanics, ETH Zürich, Zürich, Switzerland.Bone Laboratory, Hebrew University of Jerusalem, Jerusalem, Israel.Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.Bone Laboratory, Hebrew University of Jerusalem, Jerusalem, Israel.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25801536

Citation

Kogan, Natalya M., et al. "Cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 30, no. 10, 2015, pp. 1905-13.
Kogan NM, Melamed E, Wasserman E, et al. Cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts. J Bone Miner Res. 2015;30(10):1905-13.
Kogan, N. M., Melamed, E., Wasserman, E., Raphael, B., Breuer, A., Stok, K. S., Sondergaard, R., Escudero, A. V., Baraghithy, S., Attar-Namdar, M., Friedlander-Barenboim, S., Mathavan, N., Isaksson, H., Mechoulam, R., Müller, R., Bajayo, A., Gabet, Y., & Bab, I. (2015). Cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 30(10), 1905-13. https://doi.org/10.1002/jbmr.2513
Kogan NM, et al. Cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts. J Bone Miner Res. 2015;30(10):1905-13. PubMed PMID: 25801536.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts. AU - Kogan,Natalya M, AU - Melamed,Eitan, AU - Wasserman,Elad, AU - Raphael,Bitya, AU - Breuer,Aviva, AU - Stok,Kathryn S, AU - Sondergaard,Rachel, AU - Escudero,Ana V Villarreal, AU - Baraghithy,Saja, AU - Attar-Namdar,Malka, AU - Friedlander-Barenboim,Silvina, AU - Mathavan,Neashan, AU - Isaksson,Hanna, AU - Mechoulam,Raphael, AU - Müller,Ralph, AU - Bajayo,Alon, AU - Gabet,Yankel, AU - Bab,Itai, Y1 - 2015/05/10/ PY - 2014/06/04/received PY - 2015/02/15/revised PY - 2015/03/18/accepted PY - 2015/3/25/entrez PY - 2015/3/25/pubmed PY - 2016/6/21/medline KW - CANNABIDIOL KW - COLLAGEN CROSSLINKING KW - FRACTURE HEALING KW - FTIR KW - LYSYL HYDROXYLASE KW - μCT SP - 1905 EP - 13 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J Bone Miner Res VL - 30 IS - 10 N2 - Cannabinoid ligands regulate bone mass, but skeletal effects of cannabis (marijuana and hashish) have not been reported. Bone fractures are highly prevalent, involving prolonged immobilization and discomfort. Here we report that the major non-psychoactive cannabis constituent, cannabidiol (CBD), enhances the biomechanical properties of healing rat mid-femoral fractures. The maximal load and work-to-failure, but not the stiffness, of femurs from rats given a mixture of CBD and Δ(9) -tetrahydrocannabinol (THC) for 8 weeks were markedly increased by CBD. This effect is not shared by THC (the psychoactive component of cannabis), but THC potentiates the CBD stimulated work-to-failure at 6 weeks postfracture followed by attenuation of the CBD effect at 8 weeks. Using micro-computed tomography (μCT), the fracture callus size was transiently reduced by either CBD or THC 4 weeks after fracture but reached control level after 6 and 8 weeks. The callus material density was unaffected by CBD and/or THC. By contrast, CBD stimulated mRNA expression of Plod1 in primary osteoblast cultures, encoding an enzyme that catalyzes lysine hydroxylation, which is in turn involved in collagen crosslinking and stabilization. Using Fourier transform infrared (FTIR) spectroscopy we confirmed the increase in collagen crosslink ratio by CBD, which is likely to contribute to the improved biomechanical properties of the fracture callus. Taken together, these data show that CBD leads to improvement in fracture healing and demonstrate the critical mechanical role of collagen crosslinking enzymes. SN - 1523-4681 UR - https://www.unboundmedicine.com/medline/citation/25801536/Cannabidiol_a_Major_Non_Psychotropic_Cannabis_Constituent_Enhances_Fracture_Healing_and_Stimulates_Lysyl_Hydroxylase_Activity_in_Osteoblasts_ L2 - https://doi.org/10.1002/jbmr.2513 DB - PRIME DP - Unbound Medicine ER -