CB1 cannabinoid receptors mediate endochondral skeletal growth attenuation by Δ9-tetrahydrocannabinol

The endocannabinoid (EC) system regulates bone mass. Because cannabis use during pregnancy results in stature shorter than normal, we examined the role of the EC system in skeletal elongation. We show that CB1 and CB2 cannabinoid receptors are expressed specifically in hypertrophic chondrocytes of t...

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Bibliographic Details
Published in:Annals of the New York Academy of Sciences 2015-01, Vol.1335 (1), p.110-119
Main Authors: Wasserman, Elad, Tam, Joseph, Mechoulam, Raphael, Zimmer, Andreas, Maor, Gila, Bab, Itai
Format: Article
Language:English
Subjects:
Animals
Bone Development - drug effects
Bone Development - physiology
cannabinoid receptors
cannabinoids
Chondrocytes - drug effects
Chondrocytes - physiology
diacylglicerol lipases
Dronabinol - pharmacology
epiphyseal growth cartilage
Female
Femur - drug effects
Femur - growth & development
hypertrophic chondrocytes
Male
Mice, Inbred C57BL
Mice, Knockout
Receptor, Cannabinoid, CB1 - physiology
Receptor, Cannabinoid, CB2 - physiology
Spine - drug effects
Spine - growth & development
tetrahydrocannabinol
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Summary:The endocannabinoid (EC) system regulates bone mass. Because cannabis use during pregnancy results in stature shorter than normal, we examined the role of the EC system in skeletal elongation. We show that CB1 and CB2 cannabinoid receptors are expressed specifically in hypertrophic chondrocytes of the epiphyseal growth cartilage (EGC), which drives vertebrate growth. These cells also express diacylglycerol lipases, critical biosynthetic enzymes of the main EC, and 2‐arachidonoylglycerol (2‐AG), which is present at significant levels in the EGC. Femora of CB1‐ and/or CB2‐deficient mice at the end of the rapid growth phase are longer compared to wild‐type (WT) animals. We find that Δ9‐tetrahydrocannabinol (THC) slows skeletal elongation of female WT and CB2‐, but not CB1‐, deficient mice, which is reflected in femoral and lumbar vertebral body length. This in turn results in lower body weight, but unaltered fat content. THC inhibits EGC chondrocyte hypertrophy in ex vivo cultures and reduces the hypertrophic cell zone thickness of CB1‐, but not CB2‐, deficient mice. These results demonstrate a local growth‐restraining EC system in the EGC. The relevance of the present findings to humans remains to be studied.
ISSN:0077-8923
1749-6632
DOI:10.1111/nyas.12642