Sphingosylphosphorylcholine blocks ovariectomy-induced bone loss by suppressing Ca
Animals
Blotting, Western
Bone Resorption
/ drug therapy
Calcium
/ metabolism
Calmodulin
/ metabolism
Cell Survival
/ drug effects
Female
Mice
Mice, Inbred C57BL
Osteoclasts
/ drug effects
Osteoporosis
/ drug therapy
Ovariectomy
/ adverse effects
Phosphorylcholine
/ analogs & derivatives
Real-Time Polymerase Chain Reaction
Sphingosine
/ analogs & derivatives
X-Ray Microtomography
RANKL
calcineurin
osteoclast
osteoporosis
sphingosylphosphorylcholine
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
31
03
2020
revised:
29
09
2020
accepted:
01
11
2020
pubmed:
25
11
2020
medline:
1
10
2021
entrez:
24
11
2020
Statut:
ppublish
Résumé
Osteoporosis is a disease in which bone mineral density decreases due to abnormal activity of osteoclasts, and is commonly found in post-menopausal women who have decreased levels of female hormones. Sphingosylphosphorylcholine (SPC) is an important biological lipid that can be converted to sphingosine-1-phosphate (S1P) by autotaxin. S1P is known to be involved in osteoclast activation by stimulating osteoblasts, but bone regulation by SPC is not well understood. In this study, we found that SPC strongly inhibits RANKL-induced osteoclast differentiation. SPC-induced inhibitory effects on osteoclast differentiation were not affected by several antagonists of S1P receptors or pertussis toxin, suggesting cell surface receptor independency. However, SPC inhibited RANKL-induced calcineurin activation and subsequent NFATc1 activity, leading to decrease of the expression of Trap and Ctsk. Moreover, we found that bone loss in an experimental osteoporosis mouse model was recovered by SPC injection. SPC also blocked ovariectomy-induced body weight increase and Nfatc1 gene expression in mice. We also found that SPC inhibits RANKL-induced osteoclast differentiation in human macrophages. Since currently available treatments for osteoporosis, such as administration of female hormones or hormone receptor modulators, show serious side effects, SPC has potential as a new agent for osteoporosis treatment.
Identifiants
pubmed: 33230972
doi: 10.1111/jcmm.16101
pmc: PMC7810965
doi:
Substances chimiques
Calmodulin
0
sphingosine phosphorylcholine
10216-23-6
Phosphorylcholine
107-73-3
Sphingosine
NGZ37HRE42
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
473-483Subventions
Organisme : National Research Foundation of Korea
ID : NRF-2017R1A5A1014560
Organisme : National Research Foundation of Korea
ID : NRF-2018R1A2B3003868
Informations de copyright
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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