Sphingosylphosphorylcholine blocks ovariectomy‐induced bone loss by suppressing Ca2+/calmodulin‐mediated osteoclast differentiation

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 sphingos...

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Bibliographic Details
Published in:Journal of cellular and molecular medicine 2021-01, Vol.25 (1), p.473-483
Main Authors: Lee, Ha Young, Cho, Kwang Min, Kim, Min Kyung, Lee, Mingyu, Kim, Hun, Choi, Cheol Yong, Kim, Kyeong Kyu, Park, Joon Seong, Kim, Hong‐Hee, Bae, Yoe‐Sik
Format: Article
Language:English
Subjects:
calcineurin
Original
osteoclast
osteoporosis
RANKL
sphingosylphosphorylcholine
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Summary: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.
ISSN:1582-1838
1582-4934
DOI:10.1111/jcmm.16101