PKCβII-mediated cross-talk of TRPV1/CB2 modulates the glucocorticoid-induced osteoclast overactivity

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• 作者：Giulia Bellini^a ; Marco Torella^b ; Iolanda Manzo^a ; Chiara Tortora^a ; Livio Luongo^a ; Francesca Punzo^b ; Nicola Colacurci^b ; Bruno Nobili^b ; Sabatino Maione^a ; Francesca Rossi^b ; ^{francesca.rossi@unina2.it}
• 关键词：Methylprednisolone (PubChem CID ; 6741) ; Dimethyl sulfoxide (PubChem CID ; 679) ; AM630 (PubChem CID ; 4302963) ; JWH-133 (PubChem CID ; 6918505) ; RTX (PubChem CID ; 5148108)
• 刊名：Pharmacological Research
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：115
• 期：Complete
• 页码：267-274
• 全文大小：2112 K
• 卷排序：115

文摘

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.