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The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis

International Journal of Oral Science 2024年第1期16卷 154-162页

作者： Yutaro Ando Masayuki Tsukasaki Nam Cong-Nhat Huynh Shizao Zang Minglu Yan Ryunosuke Muro Kazutaka Nakamura Masatsugu Komagamine Noriko Komatsu Kazuo Okamoto Kenta Nakano Tadashi Okamura Akira Yamaguchi Kazuyuki Ishihara hiroshi takayanagi Department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Department of Microbiology Tokyo Dental College2-1-14 Kanda-Misaki-choChiyoda-kuTokyoJapan Oral Health Science Center Tokyo Dental College2-9-18Kanda-Misaki-choChiyodakuTokyoJapan Department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Unit of Prosthodontics Laboratory of Oral-Maxillofacial Biology Faculty of Odonto-StomatologyUniversity of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh CityVietnam Department of Oral and Maxillofacial Surgery Department of Sensory and Motor System MedicineGraduate School of MedicineThe University of TokyoTokyoJapan Division of Rheumatology Department of Internal MedicineKeio University School of MedicineTokyoJapan Department of Laboratory Animal Medicine Research InstituteNational Center for Global Health and MedicineTokyoJapan

The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNAsequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.

关键词： period neutrophil destruction

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Identification of an intronic enhancer regulating RANKL expression in osteocytic cells

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骨研究:英文版 2023年第3期11卷 607-616页

作者： Minglu Yan Masayuki Tsukasaki Ryunosuke Muro Yutaro Ando Kazutaka Nakamura Noriko Komatsu Takeshi Nitta Tadashi Okamura Kazuo Okamoto hiroshi takayanagi Department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoTokyoJapan Department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoTokyoJapan Department of Microbiology Tokyo Dental CollegeTokyoJapan Department of Oral and Maxillofacial Surgery Department of Sensory and Motor System MedicineGraduate School of MedicineThe University of TokyoTokyoJapan Department of Laboratory Animal Medicine Research InstituteNational Center for Global Health and MedicineTokyoJapan

The bony skeleton is continuously renewed throughout adult life by the bone remodeling process,in which old or damaged bone is removed by osteoclasts via largely unknown *** regulate bone remodeling by producing the osteoclast differentiation factor RANKL(encoded by the TNFSF11 gene).However,the precise mechanisms underlying RANKL expression in osteocytes are still ***,we explored the epigenomic landscape of osteocytic cells and identified a hitherto-undescribed osteocytic cell-specific intronic enhancer in the TNFSF11 gene *** analyses showed that transcription factors involved in cell death and senescence act on this intronic enhancer ***-cell transcriptomic data analysis demonstrated that cell death signaling increased RANKL expression in osteocytic *** deletion of the intronic enhancer led to a high-bone-mass phenotype with decreased levels of RANKL in osteocytic cells and osteoclastogenesis in the adult stage,while RANKL expression was not affected in osteoblasts or *** data suggest that osteocytes may utilize a specialized regulatory element to facilitate osteoclast formation at the bone surface to be resorbed by linking signals from cellular senescence/death and RANKL expression.

关键词： utilize removed linking

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Simultaneous augmentation of muscle and bone by locomomimetism through calcium-PGC-1αsignaling

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Bone Research 2022年第4期10卷 770-783页

作者： Takehito Ono Ryosuke Denda Yuta Tsukahara Takashi Nakamura Kazuo Okamoto hiroshi takayanagi Tomoki Nakashima Department of Cell Signaling Graduate School of Medical and Dental SciencesTokyo Medical and Dental University(TMDU)Yushima 1-5-45Bunkyo-kuTokyo 113-8549Japan Department of Orthopaedic Surgery The Jikei University School of Medicine3-25-8 Nishi-ShimbashiMinato-kuTokyo 105-8461Japan School of Dentistry Tokyo Medical and Dental University(TMDU)Yushima 1-5-45Bunkyo-kuTokyo 113-8549Japan Department of Biochemistry Tokyo Dental CollegeKandamisakicho 2-9-18Chiyoda-kuTokyo 101-0061Japan Department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoHongo 7-3-1Bunkyo-kuTokyo 113-0033Japan Department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoHongo 7-3-1Bunkyo-kuTokyo 113-0033Japan

Impaired locomotion has been extensively studied worldwide because those afflicted with it have a potential risk of becoming *** exercise at times can be an effective remedy for frailty,but exercise therapy cannot be applied in all clinical *** is safer than exercise,but there are no drugs that reinforce both muscle and bone when administered *** medications increase the risk of adverse events;thus,there is a need for individual drugs targeting both *** this end,we established a novel sequential drug screening system and identified an aminoindazole derivative,locamidazole(LAMZ),which promotes both myogenesis and osteoblastogenesis while suppressing *** of this drug enhanced locomotor function,with muscle and bone significantly ***,LAMZ induced Mef2c and PGC-1αin a calcium signaling–dependent *** this signaling is activated upon physical exercise,LAMZ mimics physical ***,LAMZ is a promising therapeutic drug for locomotor diseases,including sarcopenia and osteoporosis.

关键词： drugs clinical diseases

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Efficacy of an orally active small-molecule inhibitor of RANKL in bone metastasis

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Bone Research 2019年第1期7卷 66-75页

作者： Yuta Nakai Kazuo Okamoto Asuka Terashima Shogo Ehata Jun Nishida Takeshi Imamura Takashi Ono hiroshi takayanagi Department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoHongo 7-3-1Bunkyo-kuTokyoJapan Department of Orthodontic Science Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityYushima 1-5-45Bunkyo-kuTokyoJapan Department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoHongo 7-3-1Bunkyo-kuTokyoJapan Department of Molecular Pathology Graduate School of MedicineThe University of TokyoHongo 7-3-1Bunkyo-kuTokyoJapan Department of Molecular Medicine for Pathogenesis Ehime University Graduate School of MedicineShitsukawaToonEhimeJapan

Bone is one of the preferred sites for the metastasis of malignant tumours,such as breast cancer,lung cancer and malignant *** cells colonizing bone have the capacity to induce the expression of receptor activator of nuclear factor-κB ligand(RANKL),which promotes osteoclast differentiation and ***-induced osteoclastic bone resorption leads to a vicious cycle between tumours and bone cells that fuels osteolytic tumour growth,causing bone pain and ***,RANKL contributes to bone metastasis by acting as a chemoattractant to bone for tumour cells that express its receptor,*** inhibition of the RANKL–RANK pathway is a promising treatment for bone metastasis,and a human monoclonal anti-RANKL antibody,denosumab,has been used in the ***,orally available drugs targeting RANKL must be developed to increase the therapeutic benefits to *** we report the efficacy of the small-molecule RANKL inhibitor AS2676293 in treating bone metastasis using mouse *** administration of AS2676293 markedly inhibited bone metastasis of human breast cancer cells MDA-MB-231-5a-D-Luc2 as well as tumour-induced ***2676293 suppressed RANKLmediated tumour migration in the transwell assay and inhibited bone metastasis of the murine cell line B16F10,which is known not to trigger osteoclast *** on the results from this study,RANKL inhibition with a small-molecule compound constitutes a promising therapeutic strategy for treating bone metastasis by inhibiting both osteoclastic bone resorption and tumour migration to bone.

关键词： Bone tumours metastasis

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Brief history of the Asian International Seminars on Atomic and Molecular Physics

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原子与分子物理学报 2006年第6期23卷 1162-1163页

作者： takayanagi Kazuo Institute of Space and Astronatucial Science Professor Emeritus University of Tokyo

中日原子与分子物理讨论会是由中国著名学者清泉教授与日本著名学者高柳和夫教授共同发起创办的。第一次会议于1985年8月在成都举行。第二次会议于1988年10月在日本富士山北面脚下会议中心举行。第三次会议于1990年10月在山东泰安举... 详细信息

中日原子与分子物理讨论会是由中国著名学者清泉教授与日本著名学者高柳和夫教授共同发起创办的。第一次会议于1985年8月在成都举行。第二次会议于1988年10月在日本富士山北面脚下会议中心举行。第三次会议于1990年10月在山东泰安举行。第四次会议于1992年10月在日本东京举行。此次会议又称为第一届亚洲国际原子与分子物理讨论会。从此以后,会议规模扩大了,改称为亚洲国际原子分子论坛。现将高柳和夫教授所写的会议发展简史发表在本学报。供大家参考。

关键词：亚洲国际原子与分子物理 Brief history of the Asian International Seminars on Atomic and Molecular Physics 会议

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SOME COLLISION PROCESSES IN PLASMAS WITH HIGHER TEMPERATURE AND DENSITY

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原子与分子物理学报 1990年第4期7卷 1561-1564页

作者： Kazuo takayanagi

Some collision processes important in hot and dense plasmas are *** calculation of secondary electron velocity distribution in ionizing collision between an electron and a multiply-charged ion is reported.

关键词：等离子体高温高密度碰撞过程

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Influence of oxygen exposure on instabilities of perfluoropentacene transistor characteristics with different gate insulators

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Progress in Natural Science:Materials International 2011年第1期21卷 12-16页

作者： Hideharu UEKI Hiroaki YANO Hirokuni OHUCHI Yutaro takayanagi Yasushiro NISHIOKA Department of Precision Machinery College of Science and TechnologyNihon UniversityChiba 274-8501Japan

Pentacene for p-channel organic field effect transistors（OTFTs） and perfluoropentacene for n-channel OTFTs have attracted strong attentions to be used as CMOS type organic semiconductor materials for flexible organic displays.n-channel OTFTs with different gate insulators of polyimide（PI） and SiO2and perfluoropentacene as a semiconductor layer were fabricated,and their instability of the transistor characteristics measured in air,vacuum and oxygen was *** results show that both of the transistors exhibit a significant increase of mobility when measured in ***,the mobility of the transistors is significantly reduced when measured in pure oxygen,and the threshold voltages continuously *** phenomena may be related to water diffusion into the perfluoropentacene/gate insulator interface in air and oxidation of perfluoropentacene in oxygen.

关键词： oxygen exposure OTFT perfluoropentacene gate insulator polyimide SiO2

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Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses

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Cancer Communications 2024年第2期44卷 287-293页

作者： Kouya Shiraishi Atsushi Takahashi Yukihide Momozawa Yataro Daigo Syuzo Kaneko Takahisa Kawaguchi Hideo Kunitoh Shingo Matsumoto Hidehito Horinouchi Akiteru Goto Takayuki Honda Kimihiro Shimizu Masahiro Torasawa Daisuke takayanagi Motonobu Saito Akira Saito Yuichiro Ohe Shun-ichi Watanabe Koichi Goto Masahiro Tsuboi Katsuya Tsuchihara Sadaaki Takata Tomomi Aoi Atsushi Takano Masashi Kobayashi Yohei Miyagi Kazumi Tanaka Hiroyuki Suzuki Daichi Maeda Takumi Yamaura Maiko Matsuda Yoko Shimada Takaaki Mizuno Hiromi Sakamoto Teruhiko Yoshida Yasushi Goto Tatsuya Yoshida Taiki Yamaji Makoto Sonobe Shinichi Toyooka Kazue Yoneda Katsuhiro Masago Fumihiro Tanaka Megumi Hara Nobuo Fuse Satoshi S.Nishizuka Noriko Motoi Norie Sawada Yuichiro Nishida Kazuki Kumada Kenji Takeuchi Kozo Tanno Yasushi Yatabe Kuniko Sunami Tomoyuki Hishida Yasunari Miyazaki Hidemi Ito Mitsuhiro Amemiya Hirohiko Totsuka Haruhiko Nakayama Tomoyuki Yokose Kazuyoshi Ishigaki Toshiteru Nagashima Yoichi Ohtaki Kazuhiro Imai Ken Takasawa Yoshihiro Minamiya Kazuma Kobayashi Kenichi Okubo Kenji Wakai Atsushi Shimizu Masayuki Yamamoto Motoki Iwasaki Koichi Matsuda Johji Inazawa Yuichi Shiraishi Hiroyoshi Nishikawa Yoshinori Murakami Michiaki Kubo Fumihiko Matsuda Yoichiro Kamatani Ryuji Hamamoto Keitaro Matsuo Takashi Kohno Division of Genome Biology National Cancer Center Research InstituteTokyoJapan Department of Clinical Genomics National Cancer Center Research InstituteTokyoJapan Laboratory for Statistical Analysis Center for Integrative Medical SciencesRIKENYokohamaJapan Department of Genomic Medicine Research InstituteNational Cerebral and Cardiovascular CenterOsakaJapan Laboratory for Genotyping Development Center for Integrative Medical SciencesRIKENYokohamaJapan Center for Antibody and Vaccine Therapy Research HospitalInstitute of Medical ScienceThe University of TokyoTokyoJapan Department of Medical Oncology and Cancer Center and Center for Advanced Medicine against CancerShiga University of Medical ScienceOtsuJapan Division of Medical AI Research and Development National Cancer Center Research InstituteTokyoJapan Center for Genomic Medicine Graduate School of MedicineKyoto UniversityKyotoJapan Department of Medical Oncology Japanese Red Cross Medical CenterTokyoJapan Department of Thoracic Oncology National Cancer Center Hospital EastJapan Department of Thoracic Oncology National Cancer Center HospitalTokyoJapan Department of Cellular and Organ Pathology Graduate School of MedicineAkita UniversityAkitaJapan Department of Respiratory Medicine Tokyo Medical and Dental UniversityBunkyo-kuTokyoJapan Division of General Thoracic Surgery Department of SurgeryShinshu University School of MedicineMatsumotoNaganoJapan Department of General Surgical Science Division of General Thoracic SurgeryGunma University Graduate School of MedicineIntegrative Center of General SurgeryGunma University HospitalGunmaJapan Department of Gastrointestinal Tract Surgery Fukushima Medical University School of MedicineFukushimaJapan StaGen Co. LtdTokyoJapan Division of Thoracic Surgery National Cancer Center HospitalTokyoJapan Department of Thoracic Surgery National Cancer Center Hospital EastChibaJapan Division of Translational Informatics Exploratory Oncology Research and Clinical Trial Center(EPOC

Dear editor,Lung carcinoma is responsible for the highest fatal-ity rate among cancer-related deaths globally,with lung adenocarcinoma(LADC)emerging as the prevailing sub-type.

关键词： adenocarcinoma lung Lung

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Acute liver failure caused by drug-induced hypersensitivity syndrome associated with hyperferritinemia

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World Journal of Gastroenterology 2011年第44期17卷 4928-4931页

作者： Masayuki Miyazaki Masatake Tanaka Akihiro Ueda Tsuyoshi Yoshimoto Masaki Kato Makoto Nakamuta Kazuhiro Kotoh Ryoichi takayanagi Department of Medicine and Bioregulatory Science Graduate School of Medical ScienceKyushu University Department of Gastroenterology Kyushu Medical CenterNational Hospital Organization

Drug-induced hypersensitivity syndrome(DIHS) is a severe reaction usually characterized by fever,rash,and multiorgan failure,occurring 2-6 wk after drug *** is an immune-mediated reaction involving macrophage and T-lymphocyte activation and cytokine release.A 54-year-old woman was diagnosed with rheumatic arthritis and initiated salazosulfapyridine by *** 10 d later,she had a high fever,skin rash and liver *** was admitted to hospital and diagnosed with a drug *** was treated with oral prednisolone 30 mg/d;however,she developed high fever again and her blood tests showed acute liver failure and cytopenia associated with *** was diagnosed with acute liver failure and hemophagocytosis caused by *** was transferred to the Department of Medicine and Bioregulatory Science,Kyushu University,where she was treated with arterial steroid injection *** this treatment,her liver function improved and serum ferritin immediately *** hypothesized that an immune-mediated reaction in DIHS may have generated over-activation of macrophages and T-lymphocytes,followed by a cytokine storm that affected various *** measurement of serum ferritin might be a useful marker of the severity of DIHS.

关键词：肝功能衰竭急性药物过敏综合征 T淋巴细胞血清铁蛋白免疫反应

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ATOMIC PROCESSES IN AURORAE

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原子与分子物理学报 1985年第4期 9-11页

作者： Kazuo takayanagi Institute of Space and Astronautical Science Komaba 4-3-1 Meguro-ku Tokyo 153 Japan

Aurorae are produced in the upper atmosphere by the precipitation ofelectrons and protons from outside the atmosphere,Excitation of the visibleauroral activities is caused mainly by electrons in the energy range below... 详细信息

关键词： ATOMIC PROCESSES IN AURORAE In down

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