Kagoshima University · Graduate School of Medical and Dental Sciences · 助教

Research keywordsBMP9 signaling・osteoblast differentiation・PI3K Akt・HIF1 alpha・GSK3 beta・Hes1・SMAD signaling・bone formation

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• Ohnishi T., Nakamura T., Shima K., Noguchi K., Chiba N., Matsuguchi T. . Periodontitis promotes the expression of gingival transmembrane serine protease 2 (TMPRSS2), a priming protease for sev2022 · 記述言語： 英語 掲載種別： 研究論文（学術雑誌） 出版者・発行元： Journal of Oral Biosciences Objectives: The oral cavity is one of the main entry sites for SARS-CoV-2. Gingival keratinocytes express transmembrane serine protease 2 (TMPRSS2), responsible for priming the SARS-CoV-2 spike protein. We investigated whether periodontitis increased the expression of TMPRSS2. Methods: To investigate gene expression in periodontitis, we analyzed the expression of specific genes from (1) the Gene Expression Omnibus (GEO) dataset of 247 human gingival tissues and (2) an experimentally-induced periodontitis mouse model. Human gingival tissues with or without periodontitis were immunohistochemically stained using an anti-TMPRSS2 antibody. Analysis of the TMPRSS2 promoter was performed using a ChIP-Atlas dataset. TMPRSS2 expression was detected in cultured human keratinocytes using quantitative reverse transcription (qRT)-PCR and Western blot analysis. Results: GEO dataset analysis and an experimentally-induced periodontitis model revealed increased expression of TMPRSS2 in periodontitis gingiva. The keratinocyte cell membrane in periodontitis gingiva was strongly immunohistochemically stained for TMPRSS2. Using ChIP-Atlas and GEO datasets, we screened for transcription factors that bind to the TMPRSS2 promoter region. We found one candidate, estrogen receptor 1 (ESR1), highly expressed in periodontitis gingiva. Analysis of the GEO dataset revealed a correlation between ESR1 and TMPRSS2 expression in gingival tissues. An ESR1 ligand induced TMPRSS2 expression in cultured keratinocytes. Conclusions: Periodontitis increases TMPRSS2 expression in the cell membrane of gingival keratinocytes. DOI： 10.1016/j.job.2022.04.004 Scopus PubMed
• Ohnishi Tomokazu, Nakamura Toshiaki, Shima Kaori, Noguchi Kazuyuki, Chiba Norika, Matsuguchi Tetsuya2022 · 記述言語： 英語 出版者・発行元： (一社)歯科基礎医学会
• Nahoko Eiraku, Norika Chiba, Toshiaki Nakamura, Muhammad Subhan Amir, Chang-Hwan Seong, Tomokazu Ohnishi, Joji Kusuyama, Kazuyuki Noguchi, Tetsuya Matsuguchi . BMP9 directly induces rapid GSK32019 · 記述言語： 英語 掲載種別： 研究論文（学術雑誌） 出版者・発行元： John Wiley & Sons, Inc. Bone morphogenetic protein (BMP)9 has been reported to be the most potent BMP to induce bone formation. However, the details of BMP9‐transduced intracellular signaling remain ambiguous. Here, we have investigated signal transduction mechanisms of BMP9 in comparison to BMP2, another potent inducer of bone formation, in osteoblasts. In a mouse osteoblast cell line, BMP9 induced higher mRNA levels of alkaline phosphatase (ALP) and runt‐related transcription factor 2 (Runx2) than BMP2 within 2 h. Unlike BMP2, BMP9 induced rapid phosphorylation of glycogen synthase kinase 3‐β (GSK3‐β) and protein kinase B (Akt) and increased the cellular protein content of β‐catenin. BMP9 moderately increased mRNA levels of several canonical Wingless‐related integration site to lower degrees than BMP2. Furthermore, BMP9‐induced GSK3‐β phosphorylation was not inhibited by pretreatment with actinomycin D, cycloheximide, or Brefeldin A, indicating it is independent of Wnt protein secretion. BMP9‐induced GSK3‐β phosphorylation was abrogated by Akt or class I PI3K‐specific inhibitors. Moreover, inactivation of GSK3‐β by LiCl did not further promote ALP and Runx2 mRNA induction by BMP9 as significantly as that by BMP2. Notably, BMP9‐induced GSK3‐β phosphorylation was inhibited by small interfering RNA against endoglin and GIPC PDZ domain‐containing family, member 1. Taken together, our present findings have indicated that BMP9 directly activates GSK3β‐β‐catenin signaling pathway through class I PI3K‐Akt Axis in osteoblasts, which may be essential for the potent osteoinductive activity of BMP9. DOI： 10.1096/fj.201900733RR Scopus PubMed
• Changfu Yao, Gianni Carraro, Bindu Konda, Xiangrong Guan, Takako Mizuno, Norika Chiba, Matthew Kostelny, Adrianne Kurkciyan, Gregory David, Jonathan L McQualter, Barry R Stripp2017 · 記述言語： 英語 掲載種別： 研究論文（学術雑誌）

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