The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis

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 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

作者机构：Department of ImmunologyGraduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Department of MicrobiologyTokyo Dental College2-1-14 Kanda-Misaki-choChiyoda-kuTokyoJapan Oral Health Science CenterTokyo Dental College2-9-18Kanda-Misaki-choChiyodakuTokyoJapan Department of OsteoimmunologyGraduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Unit of ProsthodonticsLaboratory 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 SurgeryDepartment of Sensory and Motor System MedicineGraduate School of MedicineThe University of TokyoTokyoJapan Division of RheumatologyDepartment of Internal MedicineKeio University School of MedicineTokyoJapan Department of Laboratory Animal MedicineResearch InstituteNational Center for Global Health and MedicineTokyoJapan 

出 版 物：《International Journal of Oral Science》 (国际口腔科学杂志（英文版）)

年 卷 期：2024年第16卷第1期

页      面：154-162页

核心收录：

学科分类：1003[医学-口腔医学] 100302[医学-口腔临床医学] 10[医学] 

基　　金：supported in part by the Japan Agency for Medical Research and Development (AMED) under grant number JP20ek0410073, JP23ek0410108, JP22ek0410100, AMEDCREST under grant number JP19gm1210008 and AMED-PRIME under grant number JP21gm6310029, the AMED Japan Initiative for World leading Vaccine Research and Development Centers (JP223fa627001) Japan Society for the Promotion of Science (JSPS): Scientific Research S (21H05046), Scientific Research B (21H03104, 22H03195, and 22H02844) and Challenging Research (20K21515 and 21K18254) the JST FOREST Program (JPMJFR2261, JPMJFR205Z) Y.A. was supported by a JSPS Research Fellowship for Young Scientists (23KJ1949) Japanese Society for Immunology (JSI) Kibou Scholarship for Doctoral Students in Immunology 

主　　题：period neutrophil destruction 

摘      要：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.