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Cannabidiol, a major non-psychotropic cannabis constituent enhances fracture healing and stimulates lysyl hydroxylase activity in osteoblasts

Citation

Kogan, NM and Melamed, E and Wasserman, E and Raphael, B and Breuer, A and Stok, KS and Sondergaard, R and Villarreal Escudero, AV and Baraghithy, S and Attar-Namdar, M and Friedlander-Barenboim, S and Mathavan, N and Isaksson, H and Mechoulam, R and Muller, R and Bajayo, A and Gabet, Y and Bab, I, Cannabidiol, a major non-psychotropic cannabis constituent enhances fracture healing and stimulates lysyl hydroxylase activity in osteoblasts, Journal of Bone and Mineral Research, 30, (10) pp. 1905-1913. ISSN 0884-0431 (2015) [Refereed Article]

Copyright Statement

Copyright 2015 American Society for Bone and Mineral Research

DOI: doi:10.1002/jbmr.2513

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 Δ9‐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.

Item Details

Item Type:Refereed Article
Keywords:fracture healing, collagen crosslinking, lysyl hydroxylase, cannabidol, μCT, FTIR
Research Division:Engineering
Research Group:Biomedical engineering
Research Field:Biomechanical engineering
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in engineering
UTAS Author:Stok, KS (Dr Kathryn Stok)
ID Code:133643
Year Published:2015
Web of Science® Times Cited:20
Deposited By:Menzies Institute for Medical Research
Deposited On:2019-07-04
Last Modified:2019-08-13
Downloads:0

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