Tetsu Kawabata

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(-)-Epigallocatechin gallate but not chlorogenic acid suppresses EGF-stimulated migration of osteoblasts via attenuation of p38 MAPK activity

International Journal of Molecular Medicine (2018)

Tetsu Kawabata Takanobu Otsuka Kazuhiko Fujita Go Sakai Rie Matsushima‐Nishiwaki

Phenolic compounds provide health benefits in humans. A previous study by our group has indicated that the epidermal growth factor (EGF)‑induced migration of osteoblast‑like MC3T3‑E1 cells is mediated by the phosphorylation of p44/p42 mitogen‑activated protein (MAPK), p38 MAPK, stress‑activated protein kinase (SAPK)/c‑Jun N‑terminal kinase (JNK) and Akt, and that resveratrol, a major polyphenol in grape skin, suppresses the EGF‑induced migration by attenuating Akt and SAPK/JNK activation. In the present study, the effects of chlorogenic acid, a major phenolic acid in coffee, and (‑)‑epigallocatechin gallate (EGCG), a major flavonoid in green tea, on the EGF‑induced migration of MC3T3‑E1 cells were investigated. EGCG significantly reduced the EGF‑induced migration as evaluated by a Transwell migration assay and by a wound healing assay. However, chlorogenic acid failed to affect the EGF‑induced migration. The phosphorylation of p38 MAPK induced by EGF was significantly suppressed by EGCG; however, the EGF‑induced phosphorylation of p44/p42 MAP kinase, SAPK/JNK or Akt was not affected by EGCG. These results suggest that EGCG, but not chlorogenic acid, suppresses EGF‑induced osteoblast migration through inhibiting p38 MAPK activation.

10.3892/ijmm.2018.3884

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Incretins amplify TNF-α-stimulated IL-6 synthesis in osteoblasts: Suppression of the IκB/NF-κB pathway

International Journal of Molecular Medicine (2017)

Kazuhiko Fujita Haruhiko Tokuda Naohiro Yamamoto Shingo Kainuma Tetsu Kawabata

Incretins including glucagon-like peptide-1 (GLP-1) and glucose‑dependent insulinotropic polypeptide (GIP) secreted from the small intestine after oral food ingestion are currently recognized to stimulate insulin secretion from pancreatic β cells. We previously reported that p70 S6 kinase limits the tumor necrosis factor‑α (TNF‑α)‑stimulated interleukin-6 (IL‑6) synthesis in osteoblast‑like MC3T3‑E1 cells. In the present study, we investigated the effects of incretins on the TNF‑α‑induced IL‑6 synthesis and the underlying mechanism in MC3T3‑E1 cells. GLP‑1 and GIP significantly upregulated both TNF‑α‑stimulated IL‑6 release and mRNA levels. Wedelolactone, an inhibitor of IκB kinase, amplified the TNF-α-induced IL‑6 release. GLP‑1 significantly attenuated the TNF‑α‑induced phosphorylation of IκB without affecting the phosphorylation of p70 S6 kinase. On the other hand, GLP‑1 markedly induced the phosphorylation of cAMP response element-binding protein (CREB). H‑89, an inhibitor of protein kinase A, significantly suppressed the enhancement by GLP-1 of TNF-α-stimulated IL‑6 release. Dibutyryl cAMP, a permeable analogue of cAMP, which suppressed the TNF-α-induced IκB phosphorylation, amplified the IL‑6 release. These results strongly suggest that incretins upregulate the TNF-α-stimulated IL‑6 synthesis in osteoblasts, and that the amplifying effect of incretin is exerted via reducing the IκB/NF‑κB pathway through the adenylyl cyclase-cAMP system.

10.3892/ijmm.2017.2892

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Wnt3a downregulates thyroid hormone‑induced osteocalcin expression in osteoblasts

Experimental and Therapeutic Medicine (2019)

Kazuhiko Fujita Takanobu Otsuka Tetsu Kawabata Go Sakai Woo Kim

Wnt3a is a crucial modulator of bone metabolism through the canonical Wnt/β-catenin signaling pathway in bone-forming osteoblasts. We previously reported that the expression of osteocalcin is stimulated by triiodothyronine (T3) at least in part through the activation of p38 mitogen-activated protein (MAP) kinase but not p44/p42 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect of Wnt3a on the T3-induced osteocalcin expression in these cells. Wnt3a suppressed the release of osteocalcin induced by T3. The inhibitory effect of Wnt3a was dose-dependent between 0.3 and 30 ng/ml. SB216763, an inhibitor of glycogen synthase kinase-3β, that reduces the phosphorylation of β-catenin, inhibited the T3-induced osteocalcin release. Wnt3a, as well as SB216763, reduced the expression of osteocalcin mRNA induced by T3. The transcriptional activity induced by T3, assessed by a luciferase activity, was also suppressed by both Wnt3a and SB216763. In contrast, Wnt3a did not markedly affect the T3-stimulated phosphorylation of p38 MAP kinase. These results suggested that Wnt3a downregulates the T3-stimulated osteocalcin expression in MC3T3-E1 cells, and the suppressive effect of Wnt3a is independent of p38 MAP kinase.

WNT3A

10.3892/etm.2019.7764

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Enhancement by HSP90 inhibitor of PGD2-stimulated HSP27 induction in osteoblasts: Suppression of SAPK/JNK and p38 MAP kinase

Prostaglandins & Other Lipid Mediators (2019)

Woo Kim Haruhiko Tokuda Tetsu Kawabata Kazuhiko Fujita Go Sakai

Geldanamycin

Hsp27

ASK1

10.1016/j.prostaglandins.2019.03.002

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(-)-Epigallocatechin gallate synergistically potentiates prostaglandin E2-stimulated osteoprotegerin synthesis in osteoblasts

Prostaglandins & Other Lipid Mediators (2017)

Gen Kuroyanagi Haruhiko Tokuda Naohiro Yamamoto Shingo Kainuma Kazuhiko Fujita

10.1016/j.prostaglandins.2017.02.001

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Citations (11)

HSP22 (HSPB8) positively regulates PGF2α-induced synthesis of interleukin-6 and vascular endothelial growth factor in osteoblasts

Research Square (Research Square) (2020)

Gen Kuroyanagi Go Sakai Takanobu Otsuka Naohiro Yamamoto Kazuhiko Fujita

Abstract Background: Heat shock protein 22 (HSP22) belongs to class I of the small HSP family that displays ubiquitously expression including in osteoblasts. We previously demonstrated that prostaglandin F2α (PGF2α), a potent bone remodeling factor, induces the synthesis of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether HSP22 is implicated in the PGF2α-induced synthesis of IL-6 and VEGF, and the mechanism in MC3T3-E1 cells. Methods: MC3T3-E1 cells were transfected with HSP22-siRNA. IL-6 and VEGF release was assessed by ELISA. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was detected by Western blotting. Results: The PGF2α-induced release of IL-6 in HSP22 knockdown cells was significantly suppressed compared with that in the control cells. HSP22 knockdown also reduced the VEGF release by PGF2α. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was attenuated by HSP22 down-regulation. Conclusions: Our results strongly suggest that HSP22 acts as a positive regulator in the PGF2α-induced synthesis of IL-6 and VEGF in osteoblasts.

10.21203/rs.3.rs-32089/v2

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Additional file 1 of Upregulation of TGF-β-induced HSP27 by HSP90 inhibitors in osteoblasts

Figshare (2022)

Gen Kuroyanagi Haruhiko Tokuda Kazuhiko Fujita Tetsu Kawabata Go Sakai

Additional file 1 . Figure S1A, S1B, S2A, S2B, S3A, S3B, S3C, S4A, S4B, S5A, S5B, S6A and S6B show full-length gels and blots of Figure 1A, B, 2A 2B, 3A, 3B, 3C, 4A, 4B, 5A, 5B, 6A and 6B, respectively.

Hsp27

10.6084/m9.figshare.19906006

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HSP90 inhibitors potentiate PGF2α-induced IL-6 synthesis via p38 MAP kinase in osteoblasts

PLoS ONE (2017)

Kazuhiko Fujita Haruhiko Tokuda Gen Kuroyanagi Naohiro Yamamoto Shingo Kainuma

Heat shock protein 90 (HSP90) that is ubiquitously expressed in various tissues, is recognized to be a major molecular chaperone. We have previously reported that prostaglandin F2α (PGF2α), a potent bone remodeling mediator, stimulates the synthesis of interleukin-6 (IL-6) through p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells, and that Rho-kinase acts at a point upstream of p38 MAP kinase. In the present study, we investigated the involvement of HSP90 in the PGF2α-stimulated IL-6 synthesis and the underlying mechanism in MC3T3-E1 cells. Geldanamycin, an inhibitor of HSP90, significantly amplified both the PGF2α-stimulated IL-6 release and the mRNA expression levels. In addition, other HSP90 inhibitors, 17-allylamino-17demethoxy-geldanamycin (17-AAG) and 17-dimethylamino-ethylamino-17-demethoxy-geldanamycin (17-DMAG) and onalespib, enhanced the PGF2α-stimulated IL-6 release. Geldanamycin, 17-AAG and onalespib markedly strengthened the PGF2α-induced phosphorylation of p38 MAP kinase. Geldanamycin and 17-AAG did not affect the PGF2α-induced phosphorylation of p44/p42 MAP kinase and myosin phosphatase targeting subunit (MYPT-1), a substrate of Rho-kinase, and the protein levels of RhoA and Rho-kinase. In addition, HSP90-siRNA enhanced the PGF2α-induced phosphorylation of p38 MAP kinase. Furthermore, SB203580, an inhibitor of p38 MAP kinase, significantly suppressed the amplification by geldanamycin, 17-AAG or 17-DMAG of the PGF2α-stimulated IL-6 release. Our results strongly suggest that HSP90 negatively regulates the PGF2α-stimulated IL-6 synthesis in osteoblasts, and that the effect of HSP90 is exerted through regulating p38 MAP kinase activation.

Geldanamycin

10.1371/journal.pone.0177878

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Elasto-Plastic Deformation and Fatigue Fracture Behaviour of Wide Flango Beam-Columns Subjected to Diuble Curvature Cyclic Bending Under Constant Axial Load : Part X Cyclic Bending under Constant Deformation Amplitude : N/Ny=1/3,b/t=20.δ=±10mm, ±15mm, ±22.5mm

Summaries of technical papers of Annual Meeting Architectural Institute of Japan. Structures II (1985)

稔山田廣河村明勲谷 Tetsu Kawabata

Constant (computer programming)

Pure bending

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HSP22 (HSPB8) positively regulates PGF2α-induced synthesis of interleukin-6 and vascular endothelial growth factor in osteoblasts

Journal of Orthopaedic Surgery and Research (2021)

Gen Kuroyanagi Go Sakai Takanobu Otsuka Naohiro Yamamoto Kazuhiko Fujita

Abstract Background Heat shock protein 22 (HSP22) belongs to class I of the small HSP family that displays ubiquitous expression in osteoblasts. We previously demonstrated that prostaglandin F2α (PGF2α), a potent bone remodeling factor, induces the synthesis of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether HSP22 is implicated in the PGF2α-induced synthesis of IL-6 and VEGF and the mechanism of MC3T3-E1 cells. Methods MC3T3-E1 cells were transfected with HSP22-siRNA. IL-6 and VEGF release was assessed by ELISA. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was detected by Western blotting. Results The PGF2α-induced release of IL-6 in HSP22 knockdown cells was significantly suppressed compared with that in the control cells. HSP22 knockdown also reduced the VEGF release by PGF2α. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was attenuated by HSP22 downregulation. Conclusions Our results strongly suggest that HSP22 acts as a positive regulator in the PGF2α-induced synthesis of IL-6 and VEGF in osteoblasts.

10.1186/s13018-021-02209-8

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Citations (7)