The genetic ablation or pharmacological inhibition of TRPV1 signaling is beneficial in the restoration of quiescent osteoclast activity in ovariectomized mice.
Source
Department of Women, Child and of General and Specialistic Surgery, Second University of Naples, Naples, Italy.
Abstract
BACKGROUND AND PURPOSE:
Osteoporosis is a condition characterized by a decrease in the density of bone, decreasing its strength and resulting in fragile bones. The involvement of the endocannabinoid/endovanilloid system in the regulation of skeletal remodelling has been shown. The aim of this study has been to investigate the possible TRPV1-mediated regulation of bone mass in vivo and in vitro.
EXPERIMENTAL APPROACH:
A multidisciplinary approach, including biomolecular, biochemical and morphological analysis, has been used to investigate the vanilloid involvement in wild type and Trpv1-/- mice, underwent or not to ovariectomy, bone density in vivo and osteoclast activity in vitro.
KEY RESULTS:
The genetic deletion as well as the pharmacological inhibition/desensitization of the TRPV1 signalling dramatically reduced the osteoclast activity in vitro and prevented the ovariectomy-induced bone loss in vivo, together with a CB2 receptor over-expression.
CONCLUSIONS AND IMPLICATIONS:
The findings highlight a pivotal role of the TRPV1 channel in bone resorption and suggest a possible cross-talk between TRPV1 and CB2 receptor. Based on these evidence hybrid compounds acting on both TRPV1 and CB2 receptor in opposite manner could represent a future pharmacological tool in treatment of unbalanced bone remodeling-associated diseases.
This article is protected by copyright. All rights reserved.
KEYWORDS:
CB2, TRPV1, Trpv1 KO, bone remodeling, cannabinoid, menopause, osteoclasts, osteoporosis, ovariectomy, transgenic mouse, vanilloid
- PMID:
- 24308803
- [PubMed – as supplied by publisher]
