title: The genetic ablation or pharmacological inhibition of TRPV1 signalling is beneficial for the restoration of quiescent osteoclast activity in ovariectomized mice.
abstract: OBJECTIVE
  Osteoporosis is a condition characterized by a decrease in bone density, which decreases its strength and results in fragile bones. The endocannabinoid/endovanilloid system has been shown to be involved in the regulation of skeletal remodelling. The aim of this study was to investigate the possible modulation of bone mass mediated by the transient receptor potential vanilloid type 1 channel (TRPV1) in vivo and in vitro.
  
  
  METHODS
  A multidisciplinary approach, including biomolecular, biochemical and morphological analysis, was used to investigate the involvement of TRPV1 in changes in bone density in vivo and osteoclast activity in vitro, in wild-type and Trpv1(-/-) mice, that had undergone ovariectomy or had a sham operation.
  
  
  RESULTS
  Genetic deletion of Trpv1 as well as pharmacological inhibition/desensitization of TRPV1 signalling dramatically reduced the osteoclast activity in vitro and prevented the ovariectomy-induced bone loss in vivo, whereas the expression of cannabinoid type 2 (CB2 ) receptors was increased.
  
  
  CONCLUSIONS
  These findings highlight the pivotal role TRPV1 channels play in bone resorption and suggest a possible cross-talk between TRPV1 and CB2 receptors. Based on these results, hybrid compounds acting on both TRPV1 and CB2 receptors in an opposite manner could provide a future pharmacological tool for the treatment of diseases associated with disturbances in the bone remodelling process.
authors.affiliation: Department of Women, Child and of General and Specialistic Surgery, Second University of Naples, Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Rossi
authors.forename: G
authors.initials: G
authors.lastname: Bellini
authors.forename: M
authors.initials: M
authors.lastname: Torella
authors.forename: C
authors.initials: C
authors.lastname: Tortora
authors.forename: I
authors.initials: I
authors.lastname: Manzo
authors.forename: C
authors.initials: C
authors.lastname: Giordano
authors.forename: F
authors.initials: F
authors.lastname: Guida
authors.forename: L
authors.initials: L
authors.lastname: Luongo
authors.forename: F
authors.initials: F
authors.lastname: Papale
authors.forename: F
authors.initials: F
authors.lastname: Rosso
authors.forename: B
authors.initials: B
authors.lastname: Nobili
authors.forename: S
authors.initials: S
authors.lastname: Maione
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects*; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D015663:Osteoporosis, Postmenopausal / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D010052:Ovariectomy; D020239:Receptor Cross-Talk; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000172:deficiency* / Q000235:genetics
chemical_list: D050071:Bone Density Conservation Agents; C571431:Cnr2 protein, mouse; C558407:N-palmitoyl-vanillamide; D043885:Receptor, Cannabinoid, CB2; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D002211:Capsaicin
keywords: CB2 receptor; TRPV1; TRPV1 KO; bone remodelling; menopause; osteoclasts; osteoporosis; ovariectomy; transgenic mouse; vanilloids/cannabinoids