The genetic ablation or pharmacological inhibition of TRPV1 signalling is beneficial for the restoration of quiescent osteoclast activity in ovariectomized mice

• DOI: 10.1111/bph.12542
• Publication Date: 2013-12-06T11:46:44Z
• Authors: F Rossi; G Bellini; M Torella; C Tortora; I Manzo; C Giordano; F Guida; L Luongo; F Papale; F Rosso; B Nobili; S Maione
• Keywords: Mice, Knockout; 0303 health sciences; Bone Density Conservation Agents; Dose-Response Relationship, Drug; Ovariectomy; Osteoclasts; TRPV Cation Channels; Receptor Cross-Talk; Mice, Inbred C57BL; Receptor, Cannabinoid, CB2; Disease Models, Animal; 03 medical and health sciences; Bone Density; Animals; Humans; Female; Bone Remodeling; Capsaicin; Cells, Cultured; Osteoporosis, Postmenopausal; Signal Transduction

Osteoporosis is a condition characterized by decrease in bone density, which decreases its strength and results fragile bones. The endocannabinoid/endovanilloid system has been shown to be involved the regulation of skeletal remodelling. aim this study was investigate possible modulation mass mediated transient receptor potential vanilloid type 1 channel (TRPV1) vivo vitro.A multidisciplinary approach, including biomolecular, biochemical morphological analysis, used involvement TRPV1 changes density osteoclast activity vitro, wild-type Trpv1(-/-) mice, that had undergone ovariectomy or sham operation.Genetic deletion Trpv1 as well pharmacological inhibition/desensitization signalling dramatically reduced vitro prevented ovariectomy-induced loss vivo, whereas expression cannabinoid 2 (CB2 ) receptors increased.These findings highlight pivotal role channels play resorption suggest cross-talk between CB2 receptors. Based on these results, hybrid compounds acting both an opposite manner could provide future tool for treatment diseases associated with disturbances remodelling process.