Effects of vitamin D<sub>3</sub> on signaling by prostaglandin E<sub>2</sub> in osteoblast‐like cells

Tokuda, Harukuni; Kotoyori, Jun; Suzuki, Atsushi; Oiso, Yutaka; Kozawa, Osamu

doi:10.1002/jcb.240520213

Cited by 9 publications

(2 citation statements)

References 28 publications

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“…We did not observe such an interaction with 1,9-dideoxyforskolin, which does not elevate cAMP. Each of these agents may also affect processes not related to the control of intracellular cAMP levels: theophylline and pentoxyfilline raise intracellular cGMP levels (21); forskolin increases intracellular calcium concentrations and inhibits 1,25(OH)2D 3 catabolism (19); and PGE2 activates phospholipase C (26). However, the only common feature of the four agents is their ability to raise intracellular cAMP and, therefore, their interaction with 1,25(OH)2D 3 is probably due to this process.…”

Section: Discussionmentioning

confidence: 99%

1,25-Dihydroxyvitamin D3 and agents that increase intracellular adenosine 3′, 5′-monophosphate synergistically inhibit fibroblast proliferation

Saati

Ravid

Liberman

et al. 1997

In Vitro Cell.Dev.Biol.-Animal

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Agents that increase intracellular cAMP (cAMP elevating agents) and 1, 25(OH)2D3 inhibit the proliferation of many cell types. We investigated the combined effect of 1,25(OH)2D3 and cAMP elevating agents on exponentially growing mouse 3T3 fibroblasts. The following cAMP elevating agents were used: theophylline and pentoxyfilline, which inhibit cAMP-dependent phosphodiesterase; prostaglandin E2 which activates adenylate cyclase by a receptor-mediated mechanism; forskolin, which directly stimulates adenylate cyclase; and the cell permeable cAMP analogs 8-bromo cAMP and N6 benzoyl cAMP. 1,25(OH)2D3 and cAMP elevating agents were added to exponentially growing fibroblasts cultured in 96-well microtiter plates and cell number was monitored 3-7 d later. 1,25(OH)2D3 and the cAMP elevating agents as single agents inhibited the growth of the 3T3 cells. The combined treatment of the fibroblasts with 1,25(OH)2D3 and the cAMP elevating agents resulted in an antiproliferative effect that was more than additive. The synergistic interaction depended on the dose of 1,25(OH)2D3 and was apparent already at 10(-8) M of the hormone. The specificity of the effect of 1,25(OH)2D3 was demonstrated by the finding that 24,25-dihydroxyvitamin D3, a vitamin D metabolite with low affinity for the vitamin D receptor, did not affect the antiproliferative effect of cAMP elevating agents. From the synergistic interaction between 1,25(OH)2D3 and the cell permeable cAMP analogs, we infer that the site of interaction between the two signaling pathways is distal to the cAMP generating and degrading machinery.

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Section: Discussionmentioning

confidence: 99%

1,25-Dihydroxyvitamin D3 and agents that increase intracellular adenosine 3′, 5′-monophosphate synergistically inhibit fibroblast proliferation

Saati

Ravid

Liberman

et al. 1997

In Vitro Cell.Dev.Biol.-Animal

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“…TNF-alpha and AlF 4 2 have been shown to induce cAMP formation in fibroblasts [Zhang et al, 1988] and MC3T3-E1 osteoblasts [Tokuda et al, 1993], respectively. Therefore, some of their effects in this study may derive from the activation of adenylate cyclase, protein kinase A and cross-talk with PI-specific PLC coupled to other cellular receptors through multiple G proteins.…”

Section: Discussionmentioning

confidence: 99%

Protein kinases A and C positively regulate G protein-dependent activation of phosphatidylinositol-specific phospholipase C by tumor necrosis factor-alpha in MC3T3-E1 osteoblasts

Rapuano

Bockman

1997

J. Cell. Biochem.

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The role(s) of protein kinases in the regulation of G protein-dependent activation of phosphatidylinositol-specific phospholipase C by tumor necrosis factor-alpha was investigated in the osteoblast cell line MC3T3-E1. We have previously reported the stimulatory effects of tumor necrosis factor-alpha and A1F4-, an activator of G proteins, on this phospholipase pathway documented by a decrease in mass of PI and release of diacylglycerol. In this study, we further explored the mechanism(s) by which the tumor necrosis factor or A1F4(-)-promoted breakdown of phosphatidylinositol and the polyphosphoinositides by phospholipase C is regulated. Tumor necrosis factor-alpha was found to elicit a 4-5-fold increase in the formation of [3H]inositol-1,4-phosphate and [3H]inositol-1,4,5-phosphate; and a 36% increase in [3H]inositol-1-phosphate within 5 min in prelabeled cells. [3H]inositol-4-phosphate, a metabolite of [3H]inositol-1,4-phosphate and [3H]inositol-1,4,5-phosphate, was found to be the predominant phosphoinositol product of tumor necrosis factor-alpha and A1F4(-)-activated phospholipase C hydrolysis after 30 min. In addition, the preincubation of cells with pertussis toxin decreased the tumor necrosis factor-induced release of inositol phosphates by 53%. Inhibitors of protein kinase C, including Et-18-OMe and H-7, dramatically decreased the formation of [3H]inositol phosphates stimulated by either tumor necrosis factor-alpha or A1F4- by 90-100% but did not affect basal formation. The activation of cAMP-dependent protein kinase, or protein kinase A, by the treatment of cells with forskolin or 8-BrcAMP augmented basal, tumor necrosis factor-alpha and A1F4(-)-induced [3H]inositol phosphate formation. Therefore, we report that protein kinases can regulate tumor necrosis factor-alpha-initiated signalling at the cell surface in osteoblasts through effects on the coupling between receptor, G-protein and phosphatidylinositol-specific phospholipase C.

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Surface roughness modulates the response of MG63 osteoblast-like cells to 1,25-(OH)2D3 through regulation of phospholipase A2 activity and activation of protein kinase A

Lohmann

Sagun

Sylvia

et al. 1999

J. Biomed. Mater. Res.

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Implant surface roughness influences osteoblast proliferation, differentiation, and local factor production. Moreover, the responsiveness of osteoblasts to systemic hormones such as 1, 25-(OH)(2)D(3) is altered by the effects of surface roughness; on the roughest Ti surfaces the effects of roughness and 1, 25-(OH)(2)D(3) are synergistic. Prostaglandin E(2) (PGE(2)) appears to be involved in mediating the effects of surface roughness on the cells, as well as in the response to 1,25-(OH)(2)D(3). However, it is not yet known through which signaling pathways surface roughness exerts its effects on the response of osteoblasts to 1, 25-(OH)(2)D(3). The present study examined the potential role of protein kinase A (PKA), phospholipase A(2)(PLA(2)), and protein kinase C (PKC) in this process. MG63 osteoblast-like human osteosarcoma cells were cultured on cpTi disks with R(a) values of 0. 54 microm (PT), 4.14 microm (SLA), or 4.92 microm (TPS). PKA was inhibited by adding H8 to the cultures; similarly, PLA(2) was inhibited with quinacrine or activated with melittin, and PKC was inhibited with chelerythrine. Inhibitors or activators were included in the culture media through the entire culture period or for the last 24 h of culture. In addition, cultures were treated for 24 h with inhibitors or activators in the presence of 1,25-(OH)(2)D(3). The effects on cell number and alkaline phosphatase specific activity were determined after 24 h; PKC activity was determined after 9 min and at 24 h. Cell number was reduced on rough surfaces, and alkaline phosphatase activity was increased. 1,25-(OH)(2)D(3) had a synergistic effect with surface roughness on alkaline phosphatase. However, neither surface roughness nor 1,25-(OH)(2)D(3) had an effect on PKC. H8 treatment for 24 h inhibited cell number and alkaline phosphatase on all surfaces; however, when it was present throughout the culture period, the PKA inhibitor had no effect on cell number, but decreased alkaline phosphatase-specific activity. H8 reduced the 1,25-(OH)(2)D(3)-mediated effect on cell number and alkaline phosphatase. Quinacrine inhibited cell proliferation and alkaline phosphatase on all surfaces and further reduced the 1,25-(OH)(2)D(3)-dependent decreases in both parameters. Melittin had no effect when applied for 24 h and did not modify the 1,25-(OH)(2)D(3) effect; however, when present throughout the culture period, it caused a decrease in proliferation and an increase in enzyme activity. Chelerythrine, the PKC inhibitor, only inhibited cell proliferation when it was present throughout the entire culture period. However, it decreased alkaline phosphatase in cultures treated for 24 h, but increased enzyme activity when it was present for the entire culture period. The results indicate that surface roughness and 1,25-(OH)(2)D(3) both mediate their effects through PLA(2) which catalyzes the rate-limiting step in PGE(2) production. Further downstream, PGE(2) activates PKA. Surface roughness-dependent effects are also mediated through PKC, but only after the cells ha...

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Effects of vitamin D₃ on signaling by prostaglandin E₂ in osteoblast‐like cells

Cited by 9 publications

References 28 publications

1,25-Dihydroxyvitamin D3 and agents that increase intracellular adenosine 3′, 5′-monophosphate synergistically inhibit fibroblast proliferation

1,25-Dihydroxyvitamin D3 and agents that increase intracellular adenosine 3′, 5′-monophosphate synergistically inhibit fibroblast proliferation

Protein kinases A and C positively regulate G protein-dependent activation of phosphatidylinositol-specific phospholipase C by tumor necrosis factor-alpha in MC3T3-E1 osteoblasts

Surface roughness modulates the response of MG63 osteoblast-like cells to 1,25-(OH)2D3 through regulation of phospholipase A2 activity and activation of protein kinase A

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Effects of vitamin D3 on signaling by prostaglandin E2 in osteoblast‐like cells

Cited by 9 publications

References 28 publications

1,25-Dihydroxyvitamin D3 and agents that increase intracellular adenosine 3′, 5′-monophosphate synergistically inhibit fibroblast proliferation

1,25-Dihydroxyvitamin D3 and agents that increase intracellular adenosine 3′, 5′-monophosphate synergistically inhibit fibroblast proliferation

Protein kinases A and C positively regulate G protein-dependent activation of phosphatidylinositol-specific phospholipase C by tumor necrosis factor-alpha in MC3T3-E1 osteoblasts

Surface roughness modulates the response of MG63 osteoblast-like cells to 1,25-(OH)2D3 through regulation of phospholipase A2 activity and activation of protein kinase A

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Effects of vitamin D₃ on signaling by prostaglandin E₂ in osteoblast‐like cells