miR-1260bの歯周炎骨吸収抑制効果及び小胞体ストレスを介した破骨細胞分化の制御を明らかにし、その成果はインパクトの高い学術雑誌（IF=5.5）に掲載された。また、これらの研究業績が認められ、3度の学会発表受賞を果たしている。これらの成果から歯周病学への発展が認められ、本賞を受賞した。

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

The expression profiles of exosomal microRNAs (miRNAs) are regulated by the microenvironment, and appropriate priming with mesenchymal stem cells (MSCs) is one of the strategies to enhance the paracrine potency of MSCs. Our previous work demonstrated that exosomes from tumor necrosis factor (TNF)-α-primed human gingiva-derived MSCs (GMSCs) could be a therapeutic tool against periodontitis, and that TNFα-inducible exosomal miR-1260b is essential for the inhibition of alveolar bone loss. However, the precise molecular mechanism underlying miR-1260b-mediated inhibition of osteoclastogenesis is not yet fully understood. Here, we found that the activating transcription factor (ATF)-6β, a novel miR-1260b-targeting gene, is critical for the regulation of osteoclastogenesis under endoplasmic reticulum (ER) stress. An experimental periodontal mouse model demonstrated that induction of ER stress was accompanied by enhanced ATF6β expression, and local administration of miR-1260b and ATF6β siRNA using polyethylenimine nanoparticles (PEI-NPs) significantly suppressed the periodontal bone resorption. In periodontal ligament (PDL) cells, the ER stress inducer, tunicamycin, enhanced the expression of the receptor activator of NF-κB ligand (RANKL), while miR-1260b-mediated downregulation of ATF6β caused RANKL inhibition. Furthermore, the secretome from miR-1260b/ATF6β-axis-activated PDL cells inhibited osteoclastogenesis in human CD14^+ peripheral blood-derived monocytes. These results indicate that the miR-1260b/ATF6β axis mediates the regulation of ER stress, which may be used as a novel therapeutic strategy to treat periodontal disease.

DOI： 10.3389/fcell.2022.1061216

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CiNii Research

Other Link： https://www.frontiersin.org/articles/10.3389/fcell.2022.1061216/full

Repository Public URL： https://hdl.handle.net/2324/7177891

Language：English   Publishing type：Research paper (scientific journal)  

Repository Public URL： https://hdl.handle.net/2324/7161506

Language：English   Publisher：Acta Biomaterialia  

The authors regret to report that a duplicate image was published in Fig. 3D. The image of Exo-TNF Day 0 was the same as PBS Day 5. Below is a corrected full Fig. 3 with the original figure caption. This error does not affect the results of Fig. 3 or the conclusions of the study. The authors sincerely apologize for any inconvenience caused.

DOI： 10.1016/j.actbio.2024.11.029

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Publisher：Current Oral Health Reports  

Purpose of Review: Luteolin, a natural polyphenolic flavone, is a bioactive compound with high thermal stability. Owing to its prominent antioxidant activity, luteolin has been reported to exert therapeutic effects on inflammation-associated diseases. This review discusses the therapeutic potential of luteolin for treating dental diseases. Recent Findings: Luteolin has multifaceted pharmacological activities, including anti-inflammatory, neuroprotective, anticancer, and cardioprotective effects. Furthermore, the antibacterial effects of luteolin are accompanied by an anti-biofilm effect. More recently, luteolin has been identified as an inhibitor of protein kinase R (PKR), which plays an essential role in inflammasome activation. In this regard, we demonstrated the potential of luteolin as a pulp sedation compound for pulpitis that acts by suppressing PKR-mediated inflammation in dental pulp cells. Summary: Although conventional dental treatments for dental caries or periodontitis largely depend on cause-related therapy, disruption of biofilms and regulation of inflammation are prerequisites for a favorable prognosis. Together with its superior anti-inflammatory and antibacterial effects, the biocompatible features of luteolin make it a promising candidate for treating dental diseases with fewer side effects.

DOI： 10.1007/s40496-024-00389-w

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Biochemistry and Biophysics Reports  

Introduction & objectives: Stem cell therapy for regenerative medicine has been sincerely investigated, but not still popular although some clinical trials show hopeful results. This therapy is suggested to be a representative candidate such as bone defect due to the accident, iatrogenic resection oncological tumor, congenital disease, and severe periodontitis in oral region. Recently, the Bio-3D printer “Regenova®” has been introduced as an innovative three-dimensional culture system, equipped scaffold-free bio-assembling techniques without any biomaterials. Therefore, we expected a mount of bone defect could be repaired by the structure established from this Bio-3D printer using osteogenic potential stem cells. Material & methods: The gingival tissue (1x1 mm) was removed from the distal part of the lower wisdom tooth of the patients who agreed our study. Human Gingival Mesenchymal Stem Cells (hGMSCs) were isolated from this tissue and cultured, since we confirmed the characteristics such as facile isolation and accelerated proliferation, further, strong potential of osteogenic-differentiation. Spheroids were formed using hGMSC in 96-well plates designed for low cell adhesion. The size of the spheroids was measured, and fluorescent immunostaining was employed to verify the expression of stem cell and apoptosis marker, and extracellular matrix. Following four weeks of bone differentiation, μCT imaging was performed. Calcification was confirmed by alizarin red and von Kossa staining. Fluorescent immunostaining was utilized to assess the expression of markers indicative of advanced bone differentiation. Results: We have established and confirmed the spheroids (∼600 μm in diameter) constructed from human GMSCs (hGMSCs) still maintain stem cell potentials and osteogenic differentiation abilities from the results that CD73 and not CD34 were expressed as stem cell positive and negative marker, respectively. These spheroids were pilled up like cylindal shape to the “Kenzan” platform of Bio-3D printer and cultured for 7days. The cylindal structure originated from compound spheroids were tried to differentiate into bone four weeks with osteogenic induction medium. The calcification of bio-3D printed bone-like structures was confirmed by alizarin red and Von Kossa staining. In addition, μCT analysis revealed that the HU (Hounsfield Unit) of the calcified structures was almost identical to that of trabecular bone. Immunofluorescent staining detected osteocalcin expression, a late-stage bone differentiation marker. Conclusion: For the first time, we have achieved the construction of a scaffold-free, bone-like luminal structure through the assembly of spheroids comprised of this hGMSCs. This success is sure to be close to the induction of clinical application against regenerative medicine especially for bone defect disease.

DOI： 10.1016/j.bbrep.2024.101656

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Other Link： https://www.sciencedirect.com/science/article/pii/S2405580824000207?via%3Dihub

Repository Public URL： https://hdl.handle.net/2324/7174370

Event date： 2024.3

Language：English  

Venue：New Orleans, LA, USA   Country：United States  

Event date： 2022.10

Language：English  

Venue：Phoenix, AZ, USA   Country：United States  

Event date： 2021.10

Language：English  

Venue：Kyushu University   Country：Japan  

Event date： 2024.11

Language：English  

Venue：Kyushu University   Country：Japan  

Language：Japanese  

Publisher：Current Oral Health Reports  

The article Luteolin, chemical feature and potential use for oral disease, written by Takao Fukuda, Kentaro Kawakami, Masaaki Toyoda, Chikako Hayashi, Terukazu Sanui, Takeshi Uchiumi, was originally published Online First without Open Access. After publication in volume 11, issue 4, page 290 - 296 the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2024 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. The original article has been corrected.

DOI： 10.1007/s40496-025-00398-3

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