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Cannabidiol, a Major Non‐Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts

Kogan, Natalya M; Melamed, Eitan; Wasserman, Elad; Raphael, Bitya; Breuer, Aviva; Stok, Kathryn S; Sondergaard, Rachel; Escudero, Ana VVillarreal; Baraghithy, Saja and Attar‐Namdar, Malka, et al. (2015) In Journal of Bone and Mineral Research 30(10). p.1905-1913
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... (More)
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. © 2015 American Society for Bone and Mineral Research. (Less)
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keywords
μCT, FTIR, FRACTURE HEALING, COLLAGEN CROSSLINKING, LYSYL HYDROXYLASE, CANNABIDIOL
in
Journal of Bone and Mineral Research
volume
30
issue
10
pages
1905 - 1913
publisher
AMBMR
external identifiers
  • wos:000363286500019
  • scopus:84942196009
ISSN
1523-4681
DOI
10.1002/jbmr.2513
language
English
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yes
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9e1da119-9f6c-4736-bca3-2ce4d4cfd750 (old id 8147615)
date added to LUP
2015-11-02 10:11:05
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2017-07-02 03:22:57
@article{9e1da119-9f6c-4736-bca3-2ce4d4cfd750,
  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. © 2015 American Society for Bone and Mineral Research.},
  author       = {Kogan, Natalya M and Melamed, Eitan and Wasserman, Elad and Raphael, Bitya and Breuer, Aviva and Stok, Kathryn S and Sondergaard, Rachel and Escudero, Ana VVillarreal and Baraghithy, Saja and Attar‐Namdar, Malka and Friedlander‐Barenboim, Silvina and Mathavan, Neashan and Isaksson, Hanna and Mechoulam, Raphael and Müller, Ralph and Bajayo, Alon and Gabet, Yankel and Bab, Itai},
  issn         = {1523-4681},
  keyword      = {μCT,FTIR,FRACTURE HEALING,COLLAGEN CROSSLINKING,LYSYL HYDROXYLASE,CANNABIDIOL},
  language     = {eng},
  number       = {10},
  pages        = {1905--1913},
  publisher    = {AMBMR},
  series       = {Journal of Bone and Mineral Research},
  title        = {Cannabidiol, a Major Non‐Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts},
  url          = {http://dx.doi.org/10.1002/jbmr.2513},
  volume       = {30},
  year         = {2015},
}