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2. Neridronate improves bone mineral density and reduces pain in β-thalassemia patients with osteoporosis: Results from a randomized, open-label study

Author

Forni, G.L., primary, Giusti⁎, A., additional, Pinto, V., additional, Perrotta, S., additional, Borgna Pignatti, C., additional, D'Ascola, D.G., additional, Nobili, B., additional, Pitrolo, L., additional, Quarta, G., additional, Rigano, P., additional, Zanaboni, L., additional, Barone, A., additional, and Palummeri, E., additional

Published
2012
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3. The endovanilloid/endocannabinoid system: a new potential target for osteoporosis therapy.

Author

Rossi F, Bellini G, Luongo L, Torella M, Mancusi S, De Petrocellis L, Petrosino S, Siniscalco D, Orlando P, Scafuro M, Colacurci N, Perrotta S, Nobili B, Di Marzo V, and Maione S

Subjects
Acid Phosphatase metabolism, Amidohydrolases antagonists & inhibitors, Amidohydrolases genetics, Amidohydrolases metabolism, Bone and Bones metabolism, Calcium metabolism, Cell Count, Cells, Cultured, Female, Gene Expression Regulation, Gene Silencing, Humans, Immunohistochemistry, Intracellular Space metabolism, Isoenzymes metabolism, Ligands, Lipase genetics, Lipase metabolism, NF-kappa B metabolism, Osteoclasts enzymology, Osteoclasts pathology, Osteoporosis pathology, Phospholipase D genetics, Phospholipase D metabolism, Polymorphism, Single Nucleotide genetics, Postmenopause metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Receptor, Cannabinoid, CB1 antagonists & inhibitors, Receptor, Cannabinoid, CB1 genetics, Receptor, Cannabinoid, CB1 metabolism, Receptor, Cannabinoid, CB2 antagonists & inhibitors, Receptor, Cannabinoid, CB2 genetics, Receptor, Cannabinoid, CB2 metabolism, TRPV Cation Channels genetics, Tartrate-Resistant Acid Phosphatase, Cannabinoid Receptor Modulators metabolism, Endocannabinoids, Osteoporosis therapy, TRPV Cation Channels metabolism
Abstract

Human osteoclasts express functional TRPV1 channels, CB1/CB2 cannabinoid receptors and endocannabinoid/endovanilloid synthetic/catabolic enzymes. Pharmacologic manipulation of this system can modulate osteoclast activity. Here, through multidisciplinary approaches, we demonstrate that enzymes and receptors of the endocannabinoid/endovanilloid system are differently expressed in osteoclasts from menopausal women without or with osteoporosis. We report that in osteoclasts from osteoporotic patients, TRPV1 channels are upregulated and, if persistently stimulated with resiniferatoxin, become clustered to the plasma membrane while inducing a massive over-expression of CB2 receptors. By providing new evidence for a critical functional cross-talk between CB2 and TRPV1 receptors in osteoporosis, we speculate that TRPV1 desensitization, or its enhanced trafficking, together with TRPV1 agonist-induced CB2 receptor overexpression, might be critical to minimize calcium entry in osteoclasts, which could be in turn responsible of cell over-activation and higher bone resorption. Our data pave the way to the use of TRPV1 agonist together with CB2 agonists or CB1 antagonists in osteoporosis., (Copyright © 2011. Published by Elsevier Inc.)

Published
2011
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