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Sphingosylphosphorylcholine blocks ovariectomyâinduced bone loss by suppressing Ca 2+ /calmodulinâmediated osteoclast differentiation
- Source :
- Journal of Cellular and Molecular Medicine. 25:473-483
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- 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.
- Subjects :
- musculoskeletal diseases
0301 basic medicine
medicine.medical_specialty
animal structures
Pertussis toxin
03 medical and health sciences
0302 clinical medicine
Osteoclast
Cell surface receptor
Internal medicine
medicine
Receptor
biology
Chemistry
fungi
Cell Biology
Calcineurin
030104 developmental biology
Endocrinology
medicine.anatomical_structure
RANKL
030220 oncology & carcinogenesis
biology.protein
Molecular Medicine
Autotaxin
Hormone
Subjects
Details
- ISSN :
- 15824934 and 15821838
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular and Molecular Medicine
- Accession number :
- edsair.doi...........234f1e1a2d4f23174aa2e0fcd67eb03a