Sphingosine-1-phosphate-mediated osteoclast precursor monocyte migration is a critical point of control in antibone-resorptive action of active vitamin D

DOI Web Site PubMed 34 Citations 39 References
  • Junichi Kikuta
    Laboratory of Cellular Dynamics, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan;
  • Shunsuke Kawamura
    Laboratory of Cellular Dynamics, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan;
  • Fumie Okiji
    Laboratory of Cellular Dynamics, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan;
  • Mai Shirazaki
    Laboratory of Cellular Dynamics, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan;
  • Sadaoki Sakai
    Medical Affairs Division, Chugai Pharmaceutical Co., Ltd., Tokyo 103-8324, Japan
  • Hitoshi Saito
    Medical Affairs Division, Chugai Pharmaceutical Co., Ltd., Tokyo 103-8324, Japan
  • Masaru Ishii
    Laboratory of Cellular Dynamics, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan;

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<jats:p>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 CX<jats:sub>3</jats:sub>CR1<jats:sup>+</jats:sup>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.</jats:p>

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