Effects of CB2 and TRPV1 Stimulation on Osteoclast Overactivity Induced by Iron in Pediatric Inflammatory Bowel Disease.
Bone Resorption
/ metabolism
Cells, Cultured
Child
Humans
Inflammatory Bowel Diseases
/ drug therapy
Iron
/ metabolism
Iron Overload
/ metabolism
Leukocytes, Mononuclear
/ metabolism
Osteoclasts
/ metabolism
Osteoporosis
/ etiology
Receptor, Cannabinoid, CB2
/ metabolism
TRPV Cation Channels
/ metabolism
CB2
TRPV1
inflammatory bowel disease
iron metabolism
osteoclasts
osteoporosis
Journal
Inflammatory bowel diseases
ISSN: 1536-4844
Titre abrégé: Inflamm Bowel Dis
Pays: England
ID NLM: 9508162
Informations de publication
Date de publication:
01 08 2022
01 08 2022
Historique:
received:
23
09
2021
pubmed:
27
4
2022
medline:
3
8
2022
entrez:
26
4
2022
Statut:
ppublish
Résumé
The reduction of bone mineral density and osteoporosis have high impacts on the health of patients with inflammatory bowel diseases (IBD). We have previously shown that a dysregulated iron metabolism occurs in IBD and leads to a decrease in circulating iron concentration and excessive intracellular sequestration of iron. Studies suggest that iron overload significantly affects the bone, accelerating osteoclast (OC) differentiation and activation, promoting bone resorption. Moreover, we demonstrated that iron overload causes OC overactivity. The cannabinoid receptor type 2 (CB2) and the transient receptor potential vanilloid type-1 (TRPV1) are potential therapeutic targets for bone diseases. The aim of this study was to evaluate the roles of CB2 and TRPV1 receptors and of iron in the development of osteoporosis in pediatric IBD. We differentiated OCs from peripheral blood mononuclear cells of patients with IBD and healthy donors and evaluated CB2 and TRPV1 receptor expression; OC activity, and iron metabolism by Western blot, TRAP assays, bone resorption assays, and iron assays. Moreover, we analyzed the effects of the pharmacological modulation of CB2 and TRPV1 receptors on OC activity and on the iron metabolism. We confirmed the well-known roles of CB2 and TRPV1 receptors in bone metabolism and suggested that their stimulation can reduce the OC overactivity induced by iron, providing new insights into the pathogenesis of pediatric IBD-related bone resorption. Stimulation of CB2 and TRPV1 could reduce IBD-related osteoporosis due to their direct effects on OC activity and to modulating the iron metabolism. In this study, we provide new insights into the pathogenesis of inflammatory bowel disease (IBD)–related bone resorption, suggesting a role for iron. Cannabinoid receptor type 2 and transient receptor potential vanilloid type-1 stimulation could reduce IBD-related osteoporosis, directly affecting osteoclast activity and modulating iron metabolism.
Sections du résumé
BACKGROUND
The reduction of bone mineral density and osteoporosis have high impacts on the health of patients with inflammatory bowel diseases (IBD). We have previously shown that a dysregulated iron metabolism occurs in IBD and leads to a decrease in circulating iron concentration and excessive intracellular sequestration of iron. Studies suggest that iron overload significantly affects the bone, accelerating osteoclast (OC) differentiation and activation, promoting bone resorption. Moreover, we demonstrated that iron overload causes OC overactivity. The cannabinoid receptor type 2 (CB2) and the transient receptor potential vanilloid type-1 (TRPV1) are potential therapeutic targets for bone diseases. The aim of this study was to evaluate the roles of CB2 and TRPV1 receptors and of iron in the development of osteoporosis in pediatric IBD.
METHODS
We differentiated OCs from peripheral blood mononuclear cells of patients with IBD and healthy donors and evaluated CB2 and TRPV1 receptor expression; OC activity, and iron metabolism by Western blot, TRAP assays, bone resorption assays, and iron assays. Moreover, we analyzed the effects of the pharmacological modulation of CB2 and TRPV1 receptors on OC activity and on the iron metabolism.
RESULTS
We confirmed the well-known roles of CB2 and TRPV1 receptors in bone metabolism and suggested that their stimulation can reduce the OC overactivity induced by iron, providing new insights into the pathogenesis of pediatric IBD-related bone resorption.
CONCLUSIONS
Stimulation of CB2 and TRPV1 could reduce IBD-related osteoporosis due to their direct effects on OC activity and to modulating the iron metabolism.
In this study, we provide new insights into the pathogenesis of inflammatory bowel disease (IBD)–related bone resorption, suggesting a role for iron. Cannabinoid receptor type 2 and transient receptor potential vanilloid type-1 stimulation could reduce IBD-related osteoporosis, directly affecting osteoclast activity and modulating iron metabolism.
Autres résumés
Type: plain-language-summary
(eng)
In this study, we provide new insights into the pathogenesis of inflammatory bowel disease (IBD)–related bone resorption, suggesting a role for iron. Cannabinoid receptor type 2 and transient receptor potential vanilloid type-1 stimulation could reduce IBD-related osteoporosis, directly affecting osteoclast activity and modulating iron metabolism.
Identifiants
pubmed: 35472140
pii: 6574513
doi: 10.1093/ibd/izac073
pmc: PMC9340523
doi:
Substances chimiques
CNR2 protein, human
0
Receptor, Cannabinoid, CB2
0
TRPV Cation Channels
0
TRPV1 protein, human
0
Iron
E1UOL152H7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1244-1253Informations de copyright
© 2022 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.
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