Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis

Ishii, Masaru; Egen, Jackson G.; Klauschen, Frederick; Meier‐Schellersheim, Martin; Saeki, Yukihiko; Vacher, Jean; Proia, Richard L.; Germain, Ronald N.

doi:10.1038/nature07713

Cited by 479 publications

(522 citation statements)

References 29 publications

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“…Monocytes and OCPs are dynamic within BM parenchyma (Ishii et al, 2009). OCPs recirculate between BM and peripheral organs via the action of sphingosine 1-phosphate receptors (S1PRs), which attract multiple hematopoietic cell subsets from BM parenchyma into blood circulation (Walzer et al, 2007;Ishii et al, 2009Ishii et al, , 2010Pereira et al, 2010b).…”

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confidence: 99%

Oxysterols and EBI2 promote osteoclast precursor migration to bone surfaces and regulate bone mass homeostasis

Nevius¹,

Pinho²,

Dhodapkar³

et al. 2015

J Cell Biol

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Bone surfaces attract hematopoietic and nonhematopoietic cells, such as osteoclasts (OCs) and osteoblasts (OBs), and are targeted by bone metastatic cancers. However, the mechanisms guiding cells toward bone surfaces are essentially unknown. Here, we show that the Gi protein-coupled receptor (GPCR) EBI2 is expressed in mouse monocyte/OC precursors (OCPs) and its oxysterol ligand 7,25-dihydroxycholesterol (7,25-OHC) is secreted abundantly by OBs. Using in vitro time-lapse microscopy and intravital two-photon microscopy, we show that EBI2 enhances the development of large OCs by promoting OCP motility, thus facilitating cell-cell interactions and fusion in vitro and in vivo. EBI2 is also necessary and sufficient for guiding OCPs toward bone surfaces. Interestingly, OCPs also secrete 7,25-OHC, which promotes autocrine EBI2 signaling and reduces OCP migration toward bone surfaces in vivo. Defective EBI2 signaling led to increased bone mass in male mice and protected female mice from age-and estrogen deficiency-induced osteoporosis. This study identifies a novel pathway involved in OCP homing to the bone surface that may have significant therapeutic potential.

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mentioning

confidence: 99%

Oxysterols and EBI2 promote osteoclast precursor migration to bone surfaces and regulate bone mass homeostasis

Nevius¹,

Pinho²,

Dhodapkar³

et al. 2015

J Cell Biol

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“…Osteoclasts are derived from macrophage/monocyte-lineage cells that express both S1PR1 and S1PR2 (Ishii et al, 2009). As described above, S1PR1 and S1PR2 have opposite effects on the migration of osteoclast precursors.…”

Section: Osteoclast Precursors and S1pmentioning

confidence: 99%

“…1) (Ishii et al, 2009;2010). Recent advances in microscope, laser, and fluorophore technology have made it possible to visualize living cells in intact organs and to analyze their mobility and interactions in a quantitative manner.…”

Section: Application Of Intravital Imaging To the Analysis Of Cell Bementioning

confidence: 99%

“…This critical control point in osteoclastogenesis may represent an attractive target for new treatments for osteoporosis. We previously showed that treatment with FTY720, which is metabolized by SPHK2 to a compound that acts as an agonist for four of the five S1P receptors (not S1PR2) (Cyster, 2005;Matloubian et al, 2004), relieved ovariectomy-induced osteoporosis in mice by reducing the number of mature osteoclasts attached to bone surfaces (Ishii et al, 2009). The mechanism of action of S1P is completely different from that of conventional treatments such as bisphosphonates, which suppress mature osteoclasts.…”

Section: Application Of Intravital Imaging To the Analysis Of Cell Bementioning

confidence: 99%

“…One promising regulation point is the recruitment of osteoclast precursors. In addition to several chemokines that are known regulators of migration, including CXCL12 (Yu et al, 2003) and CX 3 CL1 (Koizumi et al, 2009), we have shown that sphingosine 1-phosphate (S1P), a lysophospholipid abundant in the plasma, plays an important role as both a chemoattractant and a chemorepellent (Ishii et al, 2009;2010). In this review, we summarize the bidirectional regulation of osteoclast precursor migration by S1P and briefly describe intravital bone imaging in living animals.…”

Section: Introductionmentioning

confidence: 99%

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The Role of Sphingosine 1-Phosphate in Migration of Osteoclast Precursors; an Application of Intravital Two-Photon Microscopy

Ishii

Shimazu

Nishiyama

et al. 2011

Molecules and Cells

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Sphingosine-1-phosphate (S1P), a biologically active lysophospholipid that is enriched in blood, controls the trafficking of osteoclast precursors between the circulation and bone marrow cavities via G protein-coupled receptors, S1PRs. While S1PR1 mediates chemoattraction toward S1P in bone marrow, where S1P concentration is low, S1PR2 mediates chemorepulsion in blood, where the S1P concentration is high. The regulation of precursor recruitment may represent a novel therapeutic strategy for controlling osteoclast-dependent bone remodeling. Through intravital multiphoton imaging of bone tissues, we reveal that the bidirectional function of S1P temporospatially regulates the migration of osteoclast precursors within intact bone tissues. Imaging technologies have enabled in situ visualization of the behaviors of several players in intact tissues. In addition, intravital microscopy has the potential to be more widely applied to functional analysis and intervention.

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Application of Infrared Multiphoton Microscopy in Biological Studies

Aoi¹,

Kikuta²,

Ishii³

2015

Encyclopedia of Analytical Chemistry

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Various kinds of cell types exist in the body and communicate with each other. Although there have been many previous studies of cellular dynamics in several organs, most involved conventional methods such as histological analysis and flow cytometry. These methods cannot observe dynamic cell movement in living tissues. Recently, rapid development of multiphoton microscopy has enabled us to visualize cellular dynamics deep inside living tissues and organs without thin sectioning. Focal excitation of fluorophores by simultaneous attack of multiple (normally ‘two’) photons generates images with high spatial resolution, and use of near‐infrared lasers for multiphoton excitation allows for the penetration of thicker specimens. Moreover, the minimized photobleaching and toxicity associated with multiphoton techniques allow for the imaging of living specimens for extended observation periods. Here, we focus on recent findings using intravital multiphoton imaging of dynamic biological systems, and in particular, bone homeostasis. This approach could be beneficial for understanding the mechanisms underlying dynamic biological systems, and thus useful for evaluating the efficacy and effect of novel drugs currently in development.

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Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis

Cited by 479 publications

References 29 publications

Oxysterols and EBI2 promote osteoclast precursor migration to bone surfaces and regulate bone mass homeostasis

Oxysterols and EBI2 promote osteoclast precursor migration to bone surfaces and regulate bone mass homeostasis

The Role of Sphingosine 1-Phosphate in Migration of Osteoclast Precursors; an Application of Intravital Two-Photon Microscopy

Application of Infrared Multiphoton Microscopy in Biological Studies

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