The neutrophil-osteogenic cell axis promotes bone destruction in periodontitis
10.1038/s41368-023-00275-8
- Author:
Ando YUTARO
1
,
2
,
3
;
Tsukasaki MASAYUKI
;
Huynh Cong-Nhat NAM
;
Zang SHIZAO
;
Yan MINGLU
;
Muro RYUNOSUKE
;
Nakamura KAZUTAKA
;
Komagamine MASATSUGU
;
Komatsu NORIKO
;
Okamoto KAZUO
;
Nakano KENTA
;
Okamura TADASHI
;
Yamaguchi AKIRA
;
Ishihara KAZUYUKI
;
Takayanagi HIROSHI
Author Information
1. Department of Immunology,Graduate School of Medicine and Faculty of Medicine,The University of Tokyo,Tokyo,Japan
2. Department of Microbiology,Tokyo Dental College,2-1-14 Kanda-Misaki-cho,Chiyoda-ku,Tokyo,Japan
3. Oral Health Science Center,Tokyo Dental College,Tokyo,Japan
- From:
International Journal of Oral Science
2024;16(1):154-162
- CountryChina
- Language:Chinese
-
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.
