Role of CX3CL1/Fractalkine in Osteoclast Differentiation and Bone Resorption

Koizumi, Keiichi; Saitoh, Yurika; Minami, T.; Takeno, Nobuhiro; Tsuneyama, Koichi; Miyahara, Tatsuro; Nakayama, Takashi; Sakurai, Hiroaki; Takano, Yasuo; Nishimura, Miyuki; Imai, Toshio; Yoshie, Osamu; Saiki, Ikuo

doi:10.4049/jimmunol.0803627

Cited by 129 publications

(116 citation statements)

References 37 publications

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“…In addition, CX 3 CR1, which is a cognate receptor for CX 3 CL1/fractalkine that is preferentially expressed in monocytoid cell types, is considered a good marker of osteoclast precursors (6,21,22). We sorted CSF1R-or CX 3 CR1-positive cells from CSF1R-EGFP transgenic (20) or CX 3 CR1-EGFP knockin (21) mice, respectively, and treated the sorted cells with ELD (10 −9 to 10 −8 M) in floating cultures.…”

Section: Resultsmentioning

confidence: 99%

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

Kikuta

Kawamura

Okiji

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

124

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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 3 CR1 + 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.B one is a highly dynamic organ, and it is continuously remodeled cooperatively by bone-resorbing osteoclasts and bone-replenishing osteoblasts (1). Osteoclasts, which have bone-resorbing capacity, are a unique cell type differentiated from monocyte/ macrophage lineage hematopoietic precursor cells termed osteoclast precursors. Previous studies have identified key molecular signals, such as mediated by macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL), that regulate osteoclastic differentiation and function (2, 3). Unlike osteoblasts, which are of mesenchymal origin and essentially reside in bone tissues, osteoclasts and their precursor monocytes are highly dynamic. Their migratory mechanisms in systemic circulation and homing into bone spaces have recently emerged as critical points of control for osteoclastogenesis and thus, bone homeostasis. We have recently used intravital two-photon microscopy to visualize the bone tissues of live mice and found that sphingosine-1-phosphate (S1P), a lysophospholipid mediator enriched in blood, plays a vital role in regulating the migration and positioning of osteoclast precursors on the bone surface (4, 5).Osteoclast precursor monocytes express S1PR1 (formerly designated as S1P 1 or Edg-1), a cognate receptor for S1P, and can use this receptor to migrate from bone tissues to blood that contains S1P. The deletion of S1PR1 in monocytoid cells leads to an accumulation of osteoclast precursors and a resultant increase in bone resorption, which suggests that the S1P-S1PR1 interaction is essential for the recirculation of osteoclast precursors from bone to blood (4). The expression of S1PR1 was suppressed on stimulation with RANKL, representing a reasonable mechanism wher...

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Section: Resultsmentioning

confidence: 99%

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

Kikuta

Kawamura

Okiji

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

124

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“…Expressed by osteoblastic stromal cells, it was reported to be involved in both the recruitment and attachment of osteoclast precursors (Koizumi et al, 2009). Expression of both chemokine receptors and S1PRs is reduced by RANKL stimulation, dependent on NF-κB, but not on NF-AT.…”

Section: Osteoclast Precursors and S1pmentioning

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%

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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“…Besides the already described expression of CX3CR1 (fractalkine (CX3CL1) receptor) and CCR2 (receptor for monocyte chemotactic protein 1 (MCP-1)/CCL2) [29,33,42], OCPs also express CXCR4, a receptor for stromal cell-derived factor 1 (SDF-1/CXCL12), secreted by bone marrow stromal cells, vascular endothelium and immature osteoblasts [40,41,43]. …”

Section: Murine Osteoclast Progenitorsmentioning

confidence: 99%

Induction of osteoclast progenitors in inflammatory conditions: key to bone destruction in arthritis

Šućur

Katavić

Kelava

et al. 2014

International Orthopaedics (SICOT)

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The inflammatory milieu favors recruitment and activation of osteoclasts, and leads to bone destruction as a serious complication associated with arthritis and with other inflammatory processes.The frequency and activity of osteoclast progenitors (OCPs) correspond to arthritis severity, and may be used to monitor disease progression and bone resorption, indicating the need for detailed characterization of the discrete OCP subpopulations. Collectively, current studies suggest that the most potent murine bone marrow OCP population can be identified among lymphoid negative population within the immature myeloid lineage cells, as B220 -CD3 -CD11b -/lo CD115 + CD117 + CX3CR1 + and possibly also Ter119 -CD11c -CD135 lo Ly6C + RANK -. In the peripheral blood OCP population bears the monocytoid phenotype B220 -CD3 -NK1.1 -CD11b + Ly-6C hi CD115 + CX3CR1 + , presumably expressing RANK in committed OCPs. Much less is known about human OCPs and their regulation in arthritis, but the circulating OCP subset is, most probably, comprised among the lymphoid negative population (CD3 -CD19 -CD56 -), within immature monocyte subset (CD11b + CD14 + CD16 -), expressing receptors for M-CSF and RANKL (CD115 + RANK + ). Our preliminary data confirmed positive association between the proportion of peripheral blood OCPs, defined as CD3 -CD19 -CD56 -CD11b + CD14 + , and the disease activity score (DAS28) in the follow-up samples from patient with psoriatic arthritis receiving anti-TNF therapy. In addition, we reviewed cytokines and chemokines which, directly or indirectly, activate OCPs and enhance their differentiation potential, thus mediating osteoresorption.Control of the activity and migratory behavior of OCPs as well as the identification of crucial bone/joint chemotactic mediators represent promising therapeutic targets in arthritis.Keyword: osteoclast progenitors, arthritis, inflammation, cytokines, chemokines, osteoresorption 3 Inflammation induced bone lossBone is a highly dynamic tissue important for its mechanical and metabolic functions, and characterized by rapid response to numerous physical, endocrine and paracrine stimuli in physiological and pathological conditions. Among others signals, osteoresorptive mediators (such as interleukin (IL)-1, IL-6, IL-15, IL-17, IL, 21, IL-33, tumor necrosis factor (TNF)-α and receptor activator of nuclear factor-κB ligand (RANKL), CCL2, CXCL12) produced by inflammatory/immune cells create conditions that promote maturation and function of osteoclasts [1][2][3][4]. Bone resorption and osteolysis are the prominent features and causes of substantial morbidity in inflammatory processes associated with arthritis as well as with localized bacterial infections of bone and adjacent tissues, peri-prosthetic loosening, vasculitis, connective tissue diseases, chronic viral infections and inflammatory bowel diseases [5][6][7][8]. Bone resorption in arthritisInflammatory arthritides comprise a heterogeneous group of joint disorders that are characterized by chronic inflammatory response as we...

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Role of CX3CL1/Fractalkine in Osteoclast Differentiation and Bone Resorption

Cited by 129 publications

References 37 publications

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

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

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

Induction of osteoclast progenitors in inflammatory conditions: key to bone destruction in arthritis

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