Involvement of pertussis toxin-sensitive GTP-binding protein in prostaglandin F2α-induced phosphoinositide hydrolysis in osteoblast-like cells

Miwa, Masaichi; Tokuda, Harukuni; Tsushita, Keitaro; Kotoyori, Jun; Takahashi, Yoshiyuki; Ozaki, Nobuaki; Kozawa, Osamu; Oiso, Yutaka

doi:10.1016/0006-291x(90)90817-7

Cited by 47 publications

(32 citation statements)

References 23 publications

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“…In our previous studies (18,19,22), we have shown that PGF 2␣ activates PKC through both PI-PLC and PC-PLD via heterotrimeric GTP-binding protein and that p44/p42 MAPK is activated by PGF 2␣ in a PKC-dependent manner. We here showed that bisindolylmaleimide (34) or the down-regulation of PKC suppressed the VEGF synthesis induced by PGF 2␣ .…”

Section: Effects Of Incadronate On the Phosphorylation Of Mek1/2 And mentioning

confidence: 96%

“…We also showed that the VEGF synthesis induced by NaF (40) was augmented by incadronate. We have previously reported that heterotrimeric GTP-binding protein is involved in the PGF 2␣ signaling in these cells (18,19). Therefore, it is probable that the enhancement of PGF 2␣ -induced VEGF synthesis by incadronate occurs at a point downstream from the heterotrimeric GTP-binding protein.…”

Section: Effects Of Incadronate On the Phosphorylation Of Mek1/2 And mentioning

confidence: 97%

“…We have previously reported that PGF 2␣ activates both PI-PLC and PC-PLD, known as major pathways of PKC activation (20,21), in osteoblast-like MC3T3-E1 cells (18,19). It has been reported that 24 h of pretreatment of TPA (0.1 M), a PKC-activating phorbol ester (32), down-regulates PKC in these cells (33).…”

Section: Effects Of Pkc Down-regulation or Bisindolylmaleimide On Pgfmentioning

confidence: 98%

“…We have previously reported that heterotrimeric GTP-binding protein is involved in the PGF 2␣ -induced activation of both PI-PLC and PC-PLD in osteoblast-like MC3T3-E1 cells (18,19). Thus, we investigated the effect of incadronate on the VEGF synthesis stimulated by NaF, known as a direct activator of heterotrimeric GTP-binding proteins (40).…”

Section: Effect Of Pgf 2␣ On the Translocation Of Pkc␤i To The Plasmamentioning

confidence: 99%

“…Among them, PGF 2␣ is recognized to be a potent bone-resorbing agent (17) and stimulates the proliferation and inhibits the differentiation of osteoblasts (17). In previous studies (18,19), we have demonstrated that PGF 2␣ stimulates both phosphoinositide-hydrolyzing phospholipase C (PI-PLC) and phosphatidylcholine-hydrolyzing phospholipase D (PC-PLD), recognized to be two major pathways of physiological protein kinase C (PKC) activation (20,21), in osteoblast-like MC3T3-E1 cells. We have also reported that PGF 2␣ activates p44/p42 MAPK through PKC in these cells (22).…”

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Incadronate Amplifies Prostaglandin F2α-induced Vascular Endothelial Growth Factor Synthesis in Osteoblasts

Tokuda

Harada

Hirade

et al. 2003

Journal of Biological Chemistry

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We have previously reported that prostaglandin F 2␣ (PGF 2␣ ) activates p44/p42 mitogen-activated protein kinase (MAPK) through protein kinase C (PKC) in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the mechanism of vascular endothelial growth factor (VEGF) synthesis induced by PGF 2␣ and the effect of incadronate on the VEGF synthesis in these cells. PGF 2␣ significantly stimulated the VEGF synthesis in a dose-dependent manner between 1 pM and 10 M. Cycloheximide reduced the PGF 2␣ effect. PGF 2␣ increased the levels of mRNA for VEGF. Cloprostenol, a PGF 2␣ -sensitive receptor agonist, potently induced the VEGF synthesis. Indomethacin, an inhibitor of cyclooxygenase, significantly reduced the PGF 2␣ -induced VEGF synthesis. Bisindolylmaleimide, an inhibitor of PKC, reduced the PGF 2␣ -induced VEGF synthesis. The VEGF synthesis induced by PGF 2␣ was significantly attenuated in the PKC down-regulated cells. PGF 2␣ elicited the translocation of PKC␤I from cytosol to membrane fraction. PD98059 or U0126, inhibitors of MEK, suppressed the VEGF synthesis induced by PGF 2␣ . Farnesyltransferase inhibitor failed to affect the PGF 2␣ -induced VEGF synthesis. Incadronate enhanced the synthesis of VEGF induced by PGF 2␣ . NaF-induced VEGF synthesis was also amplified by incadronate. PD98059 suppressed the enhancement by incadronate of PGF 2␣ -induced VEGF synthesis. Incadronate markedly enhanced the phosphorylation of Raf-1, MEK1/2, and p44/p42 MAPK induced by PGF 2␣ or 12-O-tetradecanoylphorbol-13-acetate, a PKC activator. Incadronate significantly enhanced the cloprostenol-increased level of VEGF concentration in mouse plasma in vivo. These results strongly suggest that PGF 2␣ stimulates VEGF synthesis through the PKC-dependent activation of p44/p42 MAPK in osteoblasts and that the incadronate enhances the VEGF synthesis at the point between PKC and Raf-1.Bone metabolism is mainly regulated by two functional cells, osteoblasts and osteoclasts; the former is responsible for bone formation, and the latter for bone resorption (1). Accumulating evidence indicates that bone-resorptive agents such as parathyroid hormone and 1,25-(OH) 2 vitamin D 3 up-regulate RANKL (receptor activator of nuclear factor B) expression through their specific receptors on osteoblasts, suggesting that osteoblasts play pivotal roles in the regulation of bone resorption (2). The bone remodeling results from the coupling bone resorption by activated osteoclasts with subsequent deposition of new matrix by osteoblasts. During the process, capillary endothelial cells provide the microvasculature, and osteoblasts and osteoprogenitor cells, which proliferate locally and differentiate into osteoblasts, migrate into the resorption lacuna.

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Section: Effects Of Incadronate On the Phosphorylation Of Mek1/2 And mentioning

confidence: 96%

Section: Effects Of Incadronate On the Phosphorylation Of Mek1/2 And mentioning

confidence: 97%

Section: Effects Of Pkc Down-regulation or Bisindolylmaleimide On Pgfmentioning

confidence: 98%

Section: Effect Of Pgf 2␣ On the Translocation Of Pkc␤i To The Plasmamentioning

confidence: 99%

mentioning

confidence: 99%

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Incadronate Amplifies Prostaglandin F2α-induced Vascular Endothelial Growth Factor Synthesis in Osteoblasts

Tokuda

Harada

Hirade

et al. 2003

Journal of Biological Chemistry

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Tiludronate inhibits interleukin-6 synthesis in osteoblasts: Inhibition of phospholipase D activation in MC3T3-E1 cells

1998

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In previous studies, we have reported that PGF2alpha stimulates phosphoinositide hydrolysis by phospholipase C and phosphatidylcholine hydrolysis by phospholipase D through heterotrimeric GTP-binding protein in osteoblast-like MC3T3-E1 cells, and that PGF2alpha and PGE1 induce interleukin-6 (IL-6) synthesis via activation of protein kinase C and protein kinase A, respectively. In the present study, we investigated the effect of tiludronate, a bisphosphonate known to inhibit bone resorption, on the PGF2alpha- and PGE1-induced IL-6 synthesis in these cells. Tiludronate significantly suppressed the PGF2alpha-induced IL-6 secretion in a dose-dependent manner in the range between 0.1 and 30 microM. However, the IL-6 secretion induced by PGE1 or (Bu)2cAMP was hardly affected by tiludronate. The choline formation induced by PGF2alpha was reduced by tiludronate dose-dependently in the range between 0.1 and 30 microM. On the contrary, tiludronate had no effect on PGF2alpha-induced formation of inositol phosphates. Tiludronate suppressed the choline formation induced by NaF, known as an activator of heterotrimeric GTP-binding protein. However, tiludronate had little effect on the formation of choline induced by TPA, a protein kinase C activator. Tiludronate significantly inhibited the NaF-induced IL-6 secretion in human osteoblastic osteosarcoma Saos-2 cells. These results strongly suggest that tiludronate inhibits PGF2alpha-induced IL-6 synthesis via suppression of phosphatidylcholine-hydrolyzing phospholipase D activation in osteoblasts, and that the inhibitory effect is exerted at the point between heterotrimeric GTP-binding protein and phospholipase D.

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Sphingosine modulates interleukin-6 synthesis in osteoblasts

1998

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We previously reported that prostaglandin (PG)E1 and PGF2alpha induce the synthesis of interleukin-6 (IL-6) via activation of protein kinase (PK)A and PKC, respectively, in osteoblast-like MC3T3-E1 cells. In addition, we have shown that basic fibroblast growth factor (bFGF) elicits IL-6 synthesis through intracellular Ca2+ mobilization in these cells and that tumor necrosis factor-alpha (TNF) induces IL-6 synthesis through sphingosine 1-phosphate produced by sphingomyelin hydrolysis. In the present study, among sphingomyelin metabolites, we examined the effect of sphingosine on IL-6 synthesis induced by various agonists in MC3T3-E1 cells. Sphingosine inhibited the IL-6 synthesis induced by PGF2alpha or 12-O-tetradecanoylphorbol-13-acetate, an activator of PKC. Sphingosine suppressed the PGE1-induced IL-6 synthesis. The IL-6 synthesis induced by cholera toxin, forskolin, or dibutyryl cAMP was inhibited by sphingosine. Sphingosine inhibited the IL-6 synthesis induced by bFGF or A23187. However, sphingosine did not affect the IL-6 synthesis induced by interleukin-1. On the contrary, sphingosine enhanced the TNF-induced IL-6 synthesis. DL-threo-Dihydrosphingosine, an inhibitor of sphingosine kinase, reduced the enhancement by sphingosine as well as the TNF-effect. These results indicate that sphingosine modulates the IL-6 synthesis stimulated by various agonists in osteoblasts.

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Involvement of pertussis toxin-sensitive GTP-binding protein in prostaglandin F2α-induced phosphoinositide hydrolysis in osteoblast-like cells

Cited by 47 publications

References 23 publications

Incadronate Amplifies Prostaglandin F2α-induced Vascular Endothelial Growth Factor Synthesis in Osteoblasts

Incadronate Amplifies Prostaglandin F2α-induced Vascular Endothelial Growth Factor Synthesis in Osteoblasts

Tiludronate inhibits interleukin-6 synthesis in osteoblasts: Inhibition of phospholipase D activation in MC3T3-E1 cells

Sphingosine modulates interleukin-6 synthesis in osteoblasts

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