title: PKCβII-mediated cross-talk of TRPV1/CB2 modulates the glucocorticoid-induced osteoclast overactivity.
abstract: In this study, we investigated the role of the endovanilloid/endocannabinoid system in the glucocorticoid-induced osteoclast overactivity. Receptorial and enzymatic component of the endovanilloid/endocannabinoid system are expressed in bone cells, and dysregulated when bone mass is reduced. Moreover, blockade or desensitization of vanilloid receptor 1 (TRPV1) and/or stimulation of cannabinoid receptor 2 (CB2) are beneficial for reducing number and activity of the bone cells modulating resorption, the osteoclasts. We have treated in vitro healthy woman derived osteoclasts with methylprednisolone in presence or not of CB2 or TRPV1 agonists/antagonists, analysing the effect on osteoclast function and morphology through a multidisciplinary approach. Moreover, a treatment with a protein kinase C inhibitor to evaluate osteoclast activity and endovanilloid/endocannabinoid component expression levels was performed in osteoclasts derived from healthy subjects in presence of not of methylprednisolone. Our results show, for the first time, that the endovanilloid/endocannabinoid system is dysregulated by the treatment with methylprednisolone, that the osteoclast activity is increased and that pharmacological compounds stimulating CB2 or inhibiting TRPV1 might reduce, possible inhibiting protein kinase C beta II, the methylprednisolone-induced osteoclast over-activation, suggesting their therapeutic use for protecting from the glucocorticoid-induced bone mass loss.
authors.affiliation: Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Bellini
authors.affiliation: Department of Woman, Child and General and Specialist Surgery, Second University of Naples, 80138 Naples, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Torella
authors.affiliation: Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy.
authors.forename: Iolanda
authors.initials: I
authors.lastname: Manzo
authors.affiliation: Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Tortora
authors.affiliation: Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy.
authors.forename: Livio
authors.initials: L
authors.lastname: Luongo
authors.affiliation: Department of Woman, Child and General and Specialist Surgery, Second University of Naples, 80138 Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Punzo
authors.affiliation: Department of Woman, Child and General and Specialist Surgery, Second University of Naples, 80138 Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Colacurci
authors.affiliation: Department of Woman, Child and General and Specialist Surgery, Second University of Naples, 80138 Naples, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Nobili
authors.affiliation: Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy.
authors.forename: Sabatino
authors.initials: S
authors.lastname: Maione
authors.affiliation: Department of Woman, Child and General and Specialist Surgery, Second University of Naples, 80138 Naples, Italy. Electronic address: francesca.rossi@unina2.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rossi
mesh_terms: D002478:Cells, Cultured; D063388:Endocannabinoids / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D064546:Protein Kinase C beta / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D063388:Endocannabinoids; D005938:Glucocorticoids; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D050916:TRPV Cation Channels; D064546:Protein Kinase C beta
keywords: AM630 (PubChem CID: 4302963); Dimethyl sulfoxide (PubChem CID: 679); Endocannabinoids; Endovanilloids; JWH-133 (PubChem CID: 6918505); Methylprednisolone (PubChem CID: 6741); Osteoclasts; Osteoporosis; RTX (PubChem CID: 5148108); Steroids