{"title":"The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis","authors":"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","doi":"10.1038/s41368-023-00275-8","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":10.8000,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Oral Science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41368-023-00275-8","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to:
Oral microbiology
Oral and maxillofacial oncology
Cariology
Oral inflammation and infection
Dental stem cells and regenerative medicine
Craniofacial surgery
Dental material
Oral biomechanics
Oral, dental, and maxillofacial genetic and developmental diseases
Craniofacial bone research
Craniofacial-related biomaterials
Temporomandibular joint disorder and osteoarthritis
The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.