2025/04/19 更新

写真a

オウ ヨウ
WENG YAO
WENG YAO
所属
医歯薬学域 助教
職名
助教
連絡先
メールアドレス

学位

  • 博士(歯学) ( 2022年3月   岡山大学 )

 

論文

  • O‐<scp>GlcNAcylation</scp> regulates osteoblast differentiation through the morphological changes in mitochondria, cytoskeleton, and endoplasmic reticulum 査読 国際共著 国際誌

    Yao Weng, Ziyi Wang, Heriati Sitosari, Mitsuaki Ono, Hirohiko Okamura, Toshitaka Oohashi

    51 ( 1 )   2024年10月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    To explore the potential mechanisms which O‐linked‐N‐acetylglucosaminylation (O‐GlcNAcylation) regulates osteogenesis, a publicly RNA‐seq dataset was re‐analyzed with literature‐mining and showed the primary targets of O‐GlcNAcylation in osteoblasts are mitochondria/cytoskeleton. Although the O‐GlcNAcylation‐regulated mitochondria/cytoskeleton has been extensively studied, its specific role during osteogenesis remains unclear. To address this, we knocked out Ogt (Ogt‐KO) in MC3T3‐E1 osteoblastic cells. Then, significantly reduced osteoblast differentiation, motility, proliferation, mitochondria–endoplasmic reticulum (Mito–ER) coupling, volume of ER, nuclear tubulins, and oxygen metabolism were observed in Ogt‐KO cells. Through artificial intelligence (AI)‐predicted cellular structures, the time‐lapse live cells imaging with reactive‐oxygen‐species/hypoxia staining showed that lower cell proliferation and altered oxygen metabolism in the Ogt‐KO cells were correlated with the Mito–ER coupling. Bioinformatics analysis, combined with correlated mRNA and protein expression, suggested that Ezh2 and its downstream targets (Opa1, Gsk3a, Wnt3a, Hif1a, and Hspa9) may be involved in O‐GlcNAcylation‐regulated Mito–ER coupling, ultimately impacting osteoblast differentiation. In conclusion, our findings indicate that O‐GlcNAcylation‐regulated osteoblast differentiation is linked to morphological changes in mitochondria, cytoskeleton, and ER, with Ezh2 potentially playing a crucial role.

    DOI: 10.1002/biof.2131

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  • O‐GlcNAcylation drives calcium signaling toward osteoblast differentiation: A bioinformatics‐oriented study

    Yao Weng, Ziyi Wang, Yoko Fukuhara, Airi Tanai, Mika Ikegame, Daisuke Yamada, Takeshi Takarada, Takashi Izawa, Satoru Hayano, Kaya Yoshida, Hiroshi Kamioka, Hirohiko Okamura

    BioFactors   2021年11月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1002/biof.1774

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  • Gingipain regulates isoform switches of PD-L1 in macrophages infected with Porphyromonas gingivalis

    Yilin Zheng, Ziyi Wang, Yao Weng, Heriati Sitosari, Yuhan He, Xiu Zhang, Noriko Shiotsu, Yoko Fukuhara, Mika Ikegame, Hirohiko Okamura

    Scientific Reports   15 ( 1 )   2025年3月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1038/s41598-025-94954-7

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    その他リンク: https://www.nature.com/articles/s41598-025-94954-7

  • PTPA localized in the Golgi apparatus plays an important role in osteoblast differentiation

    Xinyu Zheng, Yao Weng, Ayano Satoh, Airi Tanai, Mika Ikegame, Koji Kimura, Nana Yoshitani, Xiaohua Xie, Hirohiko Okamura

    Biochemical and Biophysical Research Communications   748   151329 - 151329   2025年2月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.bbrc.2025.151329

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  • High Glucose Inhibits O‐GlcNAc Transferase Translocation in Early Osteoblast Differentiation by Altering Protein Phosphatase 2A Activity 査読 国際共著 国際誌

    Heriati Sitosari, Yoko Fukuhara, Yao Weng, Yilin Zheng, Yuhan He, Xinyu Zheng, Mika Ikegame, Hirohiko Okamura

    Journal of Cellular Physiology   240 ( 1 )   2025年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/jcp.31524

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  • Filamin A mediates embryonical palatal fusion by linking mechanotransduction with β-Catenin/Smad2 査読

    Ziyi Wang, Satoru Hayano, Yao Weng, Xindi Mu, Mitsuaki Ono, Jeremie Oliver Piña, Rena N. D'Souza, Takashi Yamashiro, Toshitaka Oohashi, Hiroshi Kamioka

    2024年2月

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    出版者・発行元:Cold Spring Harbor Laboratory  

    To decipher potential mechanisms underlying cleft palate (CP), we used advanced bioinformatic integrated with literature mining and genome-wide association study (GWAS). Re-analysis of RNA-seq data (GSE45568, GSE185279) combined with literature mining highlighted the roles of Filamin A (Flna) and Epithelial-Mesenchymal Transition (EMT) in palatal development. Immunofluorescence of in vivo palatal shelves showed increased Flna in medial edge epithelial (MEE) cells and EMT cells located in an epithelial triangle. Inhibition of TGF-β or RhoA and mechanical stimuli impacted Flna expression in ex vivo cultured palatal shelves. Re-analysis of scRNA-seq data (GSE155928) highlighted a correlation between Flna and Ctnnb1 in EMT cells. Flna knockdown affected β-catenin/Smad2 expression in cultured palatal shelves and HaCaT cells. Epithelium-specific knockout of Flna delayed palatal fusion in female mice but not males. Mendelian randomization analysis suggested that parental habitual physical activity (HPA) was causally associated with lower risk of CP in their offspring. Together, these findings suggested that parental HPA could benefit their offspring's palatal development through Flna by linking mechanotransduction with the Wnt/TGF-β/Smad signaling pathways during palatal fusion.

    DOI: 10.1101/2024.02.16.580664

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  • Neuropilin 1 (NRP1) Positively Regulates Adipogenic Differentiation in C3H10T1/2 Cells 査読 国際共著 国際誌

    Yaqiong Yu, Yoko Uchida-Fukuhara, Yao Weng, Yuhan He, Mika Ikegame, Ziyi Wang, Kaya Yoshida, Hirohiko Okamura, Lihong Qiu

    24 ( 8 )   7394 - 7394   2023年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Neuropilin 1 (NRP1), a non-tyrosine kinase receptor for several ligands, is highly expressed in many kinds of mesenchymal stem cells (MSCs), but its function is poorly understood. In this study, we explored the roles of full-length NRP1 and glycosaminoglycan (GAG)-modifiable NRP1 in adipogenesis in C3H10T1/2 cells. The expression of full-length NRP1 and GAG-modifiable NRP1 increased during adipogenic differentiation in C3H10T1/2 cells. NRP1 knockdown repressed adipogenesis while decreasing the levels of Akt and ERK1/2 phosphorylation. Moreover, the scaffold protein JIP4 was involved in adipogenesis in C3H10T1/2 cells by interacting with NRP1. Furthermore, overexpression of non-GAG-modifiable NRP1 mutant (S612A) greatly promoted adipogenic differentiation, accompanied by upregulation of the phosphorylated Akt and ERK1/2. Taken together, these results indicate that NRP1 is a key regulator that promotes adipogenesis in C3H10T1/2 cells by interacting with JIP4 and activating the Akt and ERK1/2 pathway. Non-GAG-modifiable NRP1 mutant (S612A) accelerates the process of adipogenic differentiation, suggesting that GAG glycosylation is a negative post-translational modification of NRP1 in adipogenic differentiation.

    DOI: 10.3390/ijms24087394

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  • Inhibition of protein phosphatase 2A by okadaic acid induces translocation of nucleocytoplasmic O-GlcNAc transferase 査読 国際共著 国際誌

    Heriati Sitosari, Ikkei Morimoto, Yao Weng, Yilin Zheng, Yoko Fukuhara, Mika Ikegame, Hirohiko Okamura

    646   50 - 55   2023年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Post-translational modification (PTM) is crucial for many biological events, such as the modulation of bone metabolism. Phosphorylation and O-GlcNAcylation are two examples of PTMs that can occur at the same site in the protein: serine and threonine residues. This phenomenon may cause crosstalk and possible interactions between the molecules involved. Protein phosphatase 2 A (PP2A) is widely expressed throughout the body and plays a major role in dephosphorylation. At the same location where PP2A acts, O-GlcNAc transferase (OGT) can introduce uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) molecules and mediates O-GlcNAc modifications. To examine the effects of PP2A inhibition on OGT localization and expression, osteoblastic MC3T3-E1 cells were treated with Okadaic Acid (OA), a potent PP2A inhibitor. In the control cells, OGT was strictly localized in the nucleus. However, OGT was observed diffusely in the cytoplasm of the OA-treated cells. This change in localization from the nucleus to the cytoplasm resulted from an increase in mitochondrial OGT expression and translocation of the nucleocytoplasmic isoform. Furthermore, knockdown of PP2A catalytic subunit α isoform (PP2A Cα) significantly affected OGT expression (p < 0.05), and there was a correlation between PP2A Cα and OGT expression (r = 0.93). These results suggested a possible interaction between PP2A and OGT, which strengthens the notion of an interaction between phosphorylation and O-GlcNAcylation.

    Keywords: O-GlcNAc transferase; O-GlcNAcylation; Okadaic acid; Phosphorylation; Protein phosphatase 2A.

    DOI: 10.1016/j.bbrc.2023.01.033

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  • Vestigial-Like 3 Plays an Important Role in Osteoblast Differentiation by Regulating the Expression of Osteogenic Transcription Factors and BMP Signaling 査読 国際共著 国際誌

    Haoze Yuan, Mika Ikegame, Yoko Fukuhara, Fumiko Takemoto, Yaqiong Yu, Jumpei Teramachi, Yao Weng, Jiajie Guo, Daisuke Yamada, Takeshi Takarada, Ying Li, Hirohiko Okamura, Bin Zhang

    111 ( 3 )   331 - 344   2022年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Abstract
    Our previous gene profiling analysis showed that the transcription cofactor vestigial-like 3 (VGLL3) gene expression was upregulated by mechanical tension in the mouse cranial suture, coinciding with accelerated osteoblast differentiation. Therefore, we hypothesized that VGLL3 plays a significant role in osteogenic differentiation. To clarify the function of VGLL3 in osteoblasts, we examined its expression characteristics in mouse bone tissue and the osteoblastic cell line MC3T3-E1. We further examined the effects of Vgll3 knockdown on osteoblast differentiation and bone morphogenetic protein (BMP) signaling. In the mouse cranial suture, where membranous ossification occurs, VGLL3 was immunohistochemically detected mostly in the nucleus of osteoblasts, preosteoblasts, and fibroblastic cells. VGLL3 expression in MC3T3-E1 cells was transient and peaked at a relatively early stage of differentiation. RNA sequencing revealed that downregulated genes in Vgll3-knockdown cells were enriched in gene ontology terms associated with osteoblast differentiation. Interestingly, most of the upregulated genes were related to cell division. Targeted Vgll3 knockdown markedly suppressed the expression of major osteogenic transcription factors (Runx2, Sp7/osterix, and Dlx5) and osteoblast differentiation. It also attenuated BMP signaling; moreover, exogenous BMP2 partially restore osteogenic transcription factors' expression in Vgll3-knockdown cells. Furthermore, overexpression of Vgll3 increased the expression of osteogenic transcription factors. These results suggest that VGLL3 plays a critical role in promoting osteoblast differentiation and that part of the process is mediated by BMP signaling. Further elucidation of VGLL3 function will increase our understanding of osteogenesis and skeletal disease etiology.

    Keywords: BMP; Osteoblast differentiation; Transcription factors; Vestigial-like 3.

    DOI: 10.1007/s00223-022-00997-7

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    その他リンク: https://link.springer.com/article/10.1007/s00223-022-00997-7/fulltext.html

  • Outer membrane vesicles of Porphyromonas gingivalis: Novel communication tool and strategy

    Hirohiko Okamura, Katsuhiko Hirota, Kaya Yoshida, Yao Weng, Yuhan He, noriko shiotsu, Mika Ikegame, Yoko Uchida-Fukuhara, Airi Tanai, Jiajie Guo

    Japanese Dental Science Review   2021年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.jdsr.2021.07.003

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  • Extracellular vesicles of P. gingivalis-infected macrophages induce lung injury

    Kayo Yoshida, Kaya Yoshida, Natsumi Fujiwara, Mariko Seyama, Kisho Ono, Hotaka Kawai, Jiajie Guo, Ziyi Wang, Yao Weng, Yaqiong Yu, Yoko Uchida-Fukuhara, Mika Ikegame, Akira Sasaki, Hitoshi Nagatsuka, Hiroshi Kamioka, Hirohiko Okamura, Kazumi Ozaki

    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease   2021年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.bbadis.2021.166236

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  • Loading history changes the morphology and compressive force-induced expression of receptor activator of nuclear factor kappa B ligand/osteoprotegerin in MLO-Y4 osteocytes 査読 国際誌

    Ziyi Wang, Yao Weng, Yoshihito Ishihara, Naoya Odagaki, Ei Ei Hsu Hlaing, Takashi Izawa, Hirohiko Okamura, Hiroshi Kamioka

    8   e10244 - e10244   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background

    In this study, we investigated the effect of the mechanical loading history on the expression of receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) in MLO-Y4 osteocyte-like cells.

    Methods

    Three hours after MLO-Y4 osteocytes were seeded, a continuous compressive force (CCF) of 31 dynes/cm2 with or without additional CCF (32 dynes/cm2) was loaded onto the osteocytes. After 36 h, the additional CCF (loading history) was removed for a recovery period of 10 h. The expression of RANKL, OPG, RANKL/OPG ratio, cell numbers, viability and morphology were time-dependently examined at 0, 3, 6 and 10 h. Then, the same additional CCF was applied again for 1 h to all osteocytes with or without the gap junction inhibitor to examine the expression of RANKL, OPG, the RANKL/OPG ratio and other genes that essential to characterize the phenotype of MLO-Y4 cells. Fluorescence recovery after photobleaching technique was also applied to test the differences of gap-junctional intercellular communications (GJIC) among MLO-Y4 cells.

    Results

    The expression of RANKL and OPG by MLO-Y4 osteocytes without a loading history was dramatically decreased and increased, respectively, in response to the 1-h loading of additional weight. However, the expression of RANKL, OPG and the RANKL/OPG ratio were maintained at the same level as in the control group in the MLO-Y4 osteocytes with a loading history but without gap junction inhibitor treatment. Treatment of loading history significantly changed the capacity of GJIC and protein expression of connexin 43 (Cx43) but not the mRNA expression of Cx43. No significant difference was observed in the cell number or viability between the MLO-Y4 osteocyte-like cells with and without a loading history or among different time checkpoints during the recovery period. The cell morphology showed significant changes and was correlated with the expression of OPG, Gja1 and Dmp1 during the recovery period.

    Conclusion

    Our findings indicated that the compressive force-induced changes in the RANKL/OPG expression could be habituated within at least 11 h by 36-h CCF exposure. GJIC and cell morphology may play roles in response to loading history in MLO-Y4 osteocyte-like cells.

    DOI: 10.7717/peerj.10244

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    その他リンク: https://peerj.com/articles/10244.xml

  • N-(3-oxododecanoyl)-homoserine lactone regulates osteoblast apoptosis and differentiation by mediating intracellular calcium

    Jiajie Guo, Ziyi Wang, Yao Weng, Haoze Yuan, Kaya Yoshida, Mika Ikegame, Kenta Uchibe, Hiroshi Kamioka, Kazuhiko Ochiai, Hirohiko Okamura, Lihong Qiu

    Cellular Signalling   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.cellsig.2020.109740

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  • Outer membrane vesicles derived from Porphyromonas gingivalis induced cell death with disruption of tight junctions in human lung epithelial cells

    Yuhan He, Noriko Shiotsu, Yoko Uchida-Fukuhara, Jiajie Guo, Yao Weng, Mika Ikegame, Ziyi Wang, Kisho Ono, Hiroshi Kamioka, Yasuhiro Torii, Akira Sasaki, Kaya Yoshida, Hirohiko Okamura

    Archives of Oral Biology   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.archoralbio.2020.104841

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  • Outer membrane vesicles of Porphyromonas gingivalis attenuate insulin sensitivity by delivering gingipains to the liver

    Mariko Seyama, Kaya Yoshida, Kayo Yoshida, Natsumi Fujiwara, Kisho Ono, Takanori Eguchi, Hotaka Kawai, Jiajie Guo, Yao Weng, Yuan Haoze, Kenta Uchibe, Mika Ikegame, Akira Sasaki, Hitoshi Nagatsuka, Kuniaki Okamoto, Hirohiko Okamura, Kazumi Ozaki

    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.bbadis.2020.165731

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  • Inhibitory effect of retinoic acid receptor agonists on in vitro chondrogenic differentiation

    Yusuke Sumitani, Kenta Uchibe, Kaya Yoshida, Yao Weng, Jiajie Guo, Haoze Yuan, Mika Ikegame, Hiroshi Kamioka, Hirohiko Okamura

    Anatomical Science International   2020年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s12565-019-00512-3

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  • Efficacy of Glucosamine Hydrochloride Tablets combined with Sodium Hyaluronate in the treatment of Temporomandibular Joint Osteoarthritis 査読

    Jianlin Liu, Yansong Wang, Ziyi Wang, Yao Weng

    Progress in Modern Biomedicine   17 ( 2 )   331 - 333   2017年2月

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    記述言語:中国語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.13241/j.cnki.pmb.2017.02.033

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  • Optimization for landmarks-based three-dimensional cephalometric superimposition and a method for superimposition of three-dimensional image of maxilla 査読

    Yao Weng, Ziyi Wang, Xiaodong Zhang

    Chinese Journal of Medical Imaging Technology   33 ( 1 )   124 - 131   2017年1月

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    記述言語:中国語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.13929/j.1003-3289.201606089

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