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Sphingosylphosphorylcholine (SPC) is an important biological lipid that can be converted to sphingosine\u20101\u2010phosphate (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\u2010induced osteoclast differentiation. SPC\u2010induced 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\u2010induced calcineurin activation and subsequent NFATc1 activity, leading to decrease of the expression of <jats:italic>Trap<\/jats:italic> and <jats:italic>Ctsk<\/jats:italic>. Moreover, we found that bone loss in an experimental osteoporosis mouse model was recovered by SPC injection. SPC also blocked ovariectomy\u2010induced body weight increase and <jats:italic>Nfatc1<\/jats:italic> gene expression in mice. We also found that SPC inhibits RANKL\u2010induced 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.<\/jats:p>","DOI":"10.1111\/jcmm.16101","type":"journal-article","created":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T08:27:12Z","timestamp":1606206432000},"page":"473-483","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sphingosylphosphorylcholine blocks ovariectomy\u2010induced bone loss by suppressing Ca<sup>2+<\/sup>\/calmodulin\u2010mediated osteoclast differentiation"],"prefix":"10.1111","volume":"25","author":[{"given":"Ha Young","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Sungkyunkwan University Suwon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwang Min","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Sungkyunkwan University Suwon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Kyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology BK21 Program and Dental Research Institute Seoul National University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingyu","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology SAIHST Sungkyunkwan University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine Institute for Antimicrobial Resistance Research and Therapeutics Sungkyunkwan University School of Medicine Suwon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheol Yong","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Sungkyunkwan University Suwon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyeong Kyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine Institute for Antimicrobial Resistance Research and Therapeutics Sungkyunkwan University School of Medicine Suwon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joon Seong","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Hematology\u2010Oncology Ajou University School of Medicine Suwon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1411-6106","authenticated-orcid":false,"given":"Hong\u2010Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology BK21 Program and Dental Research Institute Seoul National University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6198-4512","authenticated-orcid":false,"given":"Yoe\u2010Sik","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Sungkyunkwan University Suwon Korea"},{"name":"Department of Health Sciences and Technology SAIHST Sungkyunkwan University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,11,23]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"1373","volume-title":"Williams Textbook of Endocrinology","author":"Raisz LG","year":"2002"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2008.03.027"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1593"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27071"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.262"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-019-00549-3"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030808"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199506153322401"},{"key":"e_1_2_9_10_1","unstructured":"Drugs.com. 2018.Estradiol side effects.http:\/\/www.drugs.com\/sfx\/extradiol\u2010sieeffects.html. 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