首页|The neutrophil-osteogenic cell axis promotes bone destruction in periodontitis

The neutrophil-osteogenic cell axis promotes bone destruction in periodontitis

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  • 国家科技期刊平台
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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 RNA-sequencing 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.

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

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Department of Immunology,Graduate School of Medicine and Faculty of Medicine,The University of Tokyo,Tokyo,Japan

Department of Microbiology,Tokyo Dental College,2-1-14 Kanda-Misaki-cho,Chiyoda-ku,Tokyo,Japan

Oral Health Science Center,Tokyo Dental College,Tokyo,Japan

Department of Osteoimmunology,Graduate School of Medicine and Faculty of Medicine,The University of Tokyo,Tokyo,Japan

Unit of Prosthodontics,Laboratory of Oral-Maxillofacial Biology Faculty of Odonto-Stomatology,University of Medicine and Pharmacy at Ho Chi Minh City,Ho Chi Minh City,Vietnam

Department of Oral and Maxillofacial Surgery,Department of Sensory and Motor System Medicine,Graduate School of Medicine,The University of Tokyo,Tokyo,Japan

Division of Rheumatology,Department of Internal Medicine,Keio University School of Medicine,Tokyo,Japan

Department of Laboratory Animal Medicine,Research Institute,National Center for Global Health and Medicine,Tokyo,Japan

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Japan Agency for Medical Research and Development(AMED)Japan Agency for Medical Research and Development(AMED)Japan Agency for Medical Research and Development(AMED)AMED-CRESTAMED-PRIMEAMED Japan Initiative for World leading Vaccine Research and Development CentersJapan Society for the Promotion of Science(JSPS):Scientific Research SScientific Research BScientific Research BScientific Research BChallenging ResearchChallenging ResearchJST FOREST ProgramJST FOREST ProgramJSPS Research Fellowship for Young ScientistsJapanese Society for Immunology(JSI)Kibou Scholarship for Doctoral Students in Immunology

JP20ek0410073JP23ek0410108JP22ek0410100JP19gm1210008JP21gm6310029JP223fa62700121H0504621H0310422H0319522H0284420K2151521K18254JPMJFR2261JPMJFR205Z23KJ1949

2024

10.1038/s41368-023-00275-8

国际口腔科学杂志(英文版)
四川大学

国际口腔科学杂志(英文版)

CSTPCD
影响因子：0.684
ISSN：1674-2818
年,卷(期)：2024.16(1)
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