The endovanilloid/endocannabinoid system in human osteoclasts: possible involvement in bone formation and resorption.
Recent studies suggest a role for the endocannabinoid/endovanilloid anandamide in the regulation of bone resorption/formation balance in mice. Here, we examined the co-expression of the transient receptor potential vanilloid type 1 (TRPV1) and the cannabinoid CB1/CB2 receptors together with N-acylphosphatidylethanolamine-hydrolizing phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH), the two enzymes responsible of the synthesis and catabolism of anandamide respectively, in human osteoclasts. Co-expression of TRPV1, CB1/CB2, NAPE-PLD and FAAH was found in both human osteoclast cultures and in native osteoclasts from human bone biopsies. Moreover, agonist-evoked calcium entry indicated that the TRPV1 receptor is functionally active in vitro. Consistently, biomolecular and functional experiments showed that resiniferatoxin (RTX), a selective TRPV1 receptor agonist, increased the expression and the activity of TRAP and cathepsin K, two specific osteoclast biomarkers. The evidence that cannabinoid and vanilloid receptors are co-expressed in human osteoclasts suggests that they might cross-talk to modulate the intrinsic balance of bone mineralization and resorption by different actions of anandamide through TRPV1 and cannabinoid receptors. The presence of the endocannabinoid/endovanilloid proteins in human osteoclasts will likely have implications for the management of bone demineralization associated syndrome (i. e. osteoporosis).
Rossi
F
F
Department of Pediatrics, Second University of Naples, Naples, Italy.
Siniscalco
D
D
Luongo
L
L
De Petrocellis
L
L
Bellini
G
G
Petrosino
S
S
Torella
M
M
Santoro
C
C
Nobili
B
B
Perrotta
S
S
Di Marzo
V
V
Maione
S
S
D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism; D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001862:Bone Resorption; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002211:Capsaicin / Q000378:metabolism; D056657:Cathepsin K; D002403:Cathepsins / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D063388:Endocannabinoids; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D010739:Phospholipase D / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase; D000099252:Fatty Acid Amide Hydrolases
D000135:Acid Phosphatase; D000581:Amidohydrolases; D001095:Arachidonic Acids; D002118:Calcium; D063385:Cannabinoid Receptor Modulators; D002211:Capsaicin; D056657:Cathepsin K; D002403:Cathepsins; D063388:Endocannabinoids; D007527:Isoenzymes; D010739:Phospholipase D; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D050916:TRPV Cation Channels; D000071681:Tartrate-Resistant Acid Phosphatase; D000099252:Fatty Acid Amide Hydrolases; C494484:TRPV1 receptor; C000605511:Acp5 protein, mouse; C534130:CTSK protein, human; C534132:Ctsk protein, mouse; C078814:anandamide