title: Sphingosine-1-phosphate-mediated osteoclast precursor monocyte migration is a critical point of control in antibone-resorptive action of active vitamin D.
abstract: The migration and positioning of osteoclast precursor monocytes are controlled by the blood-enriched lipid mediator sphingosine-1-phosphate (S1P) and have recently been shown to be critical points of control in osteoclastogenesis and bone homeostasis. Here, we show that calcitriol, which is the hormonally active form of vitamin D, and its therapeutically used analog, eldecalcitol, inhibit bone resorption by modulating this mechanism. Vitamin D analogs have been used clinically for treating osteoporosis, although the mode of its pharmacologic action remains to be fully elucidated. In this study, we found that active vitamin D reduced the expression of S1PR2, a chemorepulsive receptor for blood S1P, on circulating osteoclast precursor monocytes both in vitro and in vivo. Calcitriol- or eldecalcitol-treated monocytoid RAW264.7 cells, which display osteoclast precursor-like properties, migrated readily to S1P. Concordantly, the mobility of circulating CX3CR1(+) osteoclast precursor monocytes was significantly increased on systemic administration of active vitamin D. These results show a mechanism for active vitamin D in controlling the migratory behavior of circulating osteoclast precursors, and this action should be conducive to limiting osteoclastic bone resorption in vivo.
authors.affiliation: Laboratory of Cellular Dynamics, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kikuta
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kawamura
authors.forename: Fumie
authors.initials: F
authors.lastname: Okiji
authors.forename: Mai
authors.initials: M
authors.lastname: Shirazaki
authors.forename: Sadaoki
authors.initials: S
authors.lastname: Sakai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Saito
authors.forename: Masaru
authors.initials: M
authors.lastname: Ishii
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000378:metabolism*; D002117:Calcitriol / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism / Q000502:physiology*; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000081025:Sphingosine-1-Phosphate Receptors; D018709:Statistics, Nonparametric; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D050071:Bone Density Conservation Agents; D017931:DNA Primers; D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C477522:S1PR2 protein, human; D000081025:Sphingosine-1-Phosphate Receptors; D014807:Vitamin D; C060506:sphingosine 1-phosphate; D002117:Calcitriol; C547512:eldecalcitol; D013110:Sphingosine