Colony Stimulating Factor-1–Induced Osteoclast Spreading Depends on Substrate and Requires the Vitronectin Receptor and the c-<i>src</i> Proto-Oncogene

Teti, Anna; Taranta, Anna; Migliaccio, Silvia; Degiorgi, Annamaria; Santandrea, Elena; Villanova, Ida; Faraggiana, Tullio; Chellaiah, Meena; Hruska, Keith A.

doi:10.1359/jbmr.1998.13.1.50

Cited by 44 publications

(38 citation statements)

References 55 publications

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“…4A, unloading enhanced spreading of osteoclast-like cells in bone marrow cell cultures compared with that of bone marrow cell cultures obtained from loaded wild-type mice. Quantitative analyses according to the method described previously (Teti et al 1998) indicated that the maximal diameters of the osteoclastlike cells developed in the marrow cells from tail suspended wild-type mice were significantly greater than those from loaded mice in wild-type (Fig. 4B, 66 .…”

Section: Unloading Enhances Spreading Of Osteoclast-like Cells and Thmentioning

confidence: 85%

“…Mature osteoclasts also contain the M-CSF receptor, c-fms, which is required for the survival, spreading, and migration of these cells. It has been revealed that M-CSF induces spreading of osteoclasts , Teti et al 1998, Grey et al 2000. This effect of M-CSF requires the integrity of the a v b 3 integrin and signals through the c-fms, non-receptor type tyrosine kinase, c-src, phosphatidylinositol 3-kinase, and phospholipase Cg , Ducy et al 2000, Nakamura et al 2001, Sanjay et al 2001).…”

Section: Discussionmentioning

confidence: 99%

“…After rinsing the samples with water, the number of TRAP-positive multinucleated (cells containing more than two nuclei) osteoclast-like cells was counted under a light microscope. Quantitative analysis of the cell spreading was conducted according to the method described previously (Teti et al 1998). After taking the micrographs of the cells, the cell maximal diameter (stretch) was measured by using a Luzex-F automated image analysis system (NIRECO).…”

Section: Osteoclast-like Tartrate-resistant Acid Phosphatase (Trap)-pmentioning

confidence: 99%

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Osteopontin is required for mechanical stress-dependent signals to bone marrow cells

Ishijima¹,

Tsuji²,

Rittling³

et al. 2007

Journal of Endocrinology

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Mechanical stress to bone plays a crucial role in the maintenance of bone homeostasis. It causes the deformation of bone matrix and generates strain force, which could initiate the mechanotransduction pathway. The presence of osteopontin (OPN), which is one of the abundant proteins in bone matrix, is required for the effects of mechanical stress on bone, as we have reported that OPN-null (OPNK/K) mice showed resistance to unloading-induced bone loss. However, cellular mechanisms underlying the phenomenon have not been completely elucidated. To obtain further insight into the role of OPN in mediating mechanical stress effect on bone, we examined in vitro mineralization and osteoclast-like cell formation in bone marrow cells obtained from hind limb bones of OPNK/K mice after tail suspension. The levels of mineralized nodule formation of bone marrow cells derived from the femora subjected to unloading were decreased compared with that from loaded control in wild-type mice. However, these were not decreased in cells from OPNK/K mice after tail suspension compared with that from loaded OPNK/K mice. Moreover, while spreading of osteoclast-like cells derived from bone marrow cells of the femora subjected to unloading was enhanced compared with that from loaded control in wild-type mice, this enhancement of spreading of these cells derived from the femora subjected to unloading was not recognized compared with those from loaded control in OPNK/K mice. These data provided cellular bases for the effect of the OPN deficiency on in vitro reduced mineralized nodule formation by osteoblasts and on enhancement of osteoclast spreading in vitro induced by the absence of mechanical stress. These in vitro results correlate well with the resistance to unloading-induced bone loss in OPNK/K mice in vivo, suggesting that OPN has an important role in the effects of unloading-induced alterations of differentiation of bone marrow into osteoblasts and osteoclasts.

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Section: Unloading Enhances Spreading Of Osteoclast-like Cells and Thmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Osteoclast-like Tartrate-resistant Acid Phosphatase (Trap)-pmentioning

confidence: 99%

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Osteopontin is required for mechanical stress-dependent signals to bone marrow cells

Ishijima¹,

Tsuji²,

Rittling³

et al. 2007

Journal of Endocrinology

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“…Mice, in which the c-src gene has been disrupted, show normal osteoclast development, but bone resorption is impaired (38). c-Src participates in the formation of the ruffled border (39), but it is also required for spreading of osteoclasts induced by CSF-1 (40,41). In avian osteoclasts, c-Src is involved in the activation of PI 3-K induced by osteopontin, a matrix protein that binds to the integrin a v b 3 (42).…”

Section: Discussionmentioning

confidence: 99%

The role of phosphoinositide 3-kinase in spreading osteoclasts induced by colony-stimulating factor-1

Palacio

Félix

2001

European Journal of Endocrinology

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Background: Colony-stimulating factor-1 (CSF-1), a growth and survival factor for osteoclasts, stimulates these cells to spread and migrate towards a gradient of CSF-1. This may support the translocation of osteoclasts to new sites on the bone surface to be resorbed. Phosphoinositide 3-kinase (PI 3-K) is a lipid kinase participating in various signal transduction pathways. Objective: To investigate the role of PI 3-K in the CSF-1-induced spreading of osteoclasts. Methods: In isolated rat osteoclasts treated with or without CSF-1, the distribution of PI 3-K and proteins phosphorylated on tyrosine were investigated using immunofluorescence. In murine osteoclast-like cells grown from bone marrow cells co-cultured with osteoblasts, the activation of the PI 3-K by CSF-1 was determined both in vivo and in vitro. In vivo, the enzyme product in the cell was determined after extraction and separation with thin layer chromatography; in vitro, PI 3-K activity was measured in the pellet immunoprecipitated from the cell lysate. Results: Inhibition of PI 3-K blocked the CSF-1-induced spreading of osteoclasts. In spreading osteoclasts, a portion of PI 3-K was translocated to the periphery where proteins phosphorylated on tyrosine appeared simultaneously. In osteoclast-like cells, CSF-1 stimulated PI 3-K activity. This activity could be immunoprecipitated with antibody against phophotyrosine residues. Conclusion: PI 3-K participates in the CSF-1-induced spreading of osteoclasts. The activated PI 3-K may induce the reorganization of the cytoskeleton resulting in spreading and migration.

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“…NFATc1 is a master regulator of OCL differentiation through the Ca 2+ /calmodulin/calcineurindependent pathway (24). c-Src is a non-receptor-type tyrosine kinase that regulates the formation of actin-rich podosomes in the OCLs (25). Cathepsin K is an OCLspecific lysosomal cysteine proteinase (26).…”

Section: Effects Of Fisetin On the Expression Levels Of Ocl Marker Prmentioning

confidence: 99%

Fisetin Inhibits Osteoclastogenesis Through Prevention of RANKL-Induced ROS Production by Nrf2-Mediated Up-regulation of Phase II Antioxidant Enzymes

et al. 2013

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Abstract. Osteoclasts (OCLs) are multinucleated bone-resorbing cells that are differentiated by stimulation with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor. We recently demonstrated that regulation of heme-oxygenase 1 (HO-1), a stress-induced cytoprotective enzyme, also functions in OCL differentiation. In this study, we investigated effects of fisetin, a natural bioactive flavonoid that has been reported to induce HO-1 expression, on the differentiation of macrophages into OCLs. Fisetin inhibited the formation of OCLs in a dose-dependent manner and suppressed the bone-resorbing activity of OCLs. Moreover, fisetin-treated OCLs showed markedly decreased phosphorylation of extracellular signal-regulated kinase, Akt, and Jun N-terminal kinase, but fisetin did not inhibit p38 phosphorylation. Fisetin up-regulated mRNA expression of phase II antioxidant enzymes including HO-1 and interfered with RANKL-mediated reactive oxygen species (ROS) production. Studies with RNA interference showed that suppression of NF-E2-related factor 2 (Nrf2), a key transcription factor for phase II antioxidant enzymes, rescued fisetin-mediated inhibition of OCL differentiation. Furthermore, fisetin significantly decreased RANKL-induced nuclear translocation of cFos and nuclear factor of activated T cells cytoplasmic-1 (NFATc1), which is a transcription factor critical for osteoclastogenic gene regulation. Therefore, fisetin inhibits OCL differentiation through blocking RANKLmediated ROS production by Nrf2-mediated up-regulation of phase II antioxidant enzymes.

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Colony Stimulating Factor-1–Induced Osteoclast Spreading Depends on Substrate and Requires the Vitronectin Receptor and the c-src Proto-Oncogene

Cited by 44 publications

References 55 publications

Osteopontin is required for mechanical stress-dependent signals to bone marrow cells

Osteopontin is required for mechanical stress-dependent signals to bone marrow cells

The role of phosphoinositide 3-kinase in spreading osteoclasts induced by colony-stimulating factor-1

Fisetin Inhibits Osteoclastogenesis Through Prevention of RANKL-Induced ROS Production by Nrf2-Mediated Up-regulation of Phase II Antioxidant Enzymes

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