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

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          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.

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          Author and article information

          Journal
          Proc. Natl. Acad. Sci. U.S.A.
          Proceedings of the National Academy of Sciences of the United States of America
          1091-6490
          0027-8424
          Apr 23 2013
          : 110
          : 17
          Affiliations
          [1 ] Laboratory of Cellular Dynamics, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
          Article
          1218799110
          10.1073/pnas.1218799110
          3637769
          23569273
          3823ee46-0e1a-48ff-b936-71bb53245bd5
          History

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