The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
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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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.

Abstract Image

中性粒细胞-成骨细胞轴促进牙周炎中的骨质破坏
免疫细胞与基质细胞之间的相互作用在健康和疾病中发挥着关键作用。牙周炎是人类最常见的传染性疾病,免疫细胞聚集在口腔黏膜中,通过诱导成骨细胞(如成骨细胞和牙周韧带细胞)中核因子κB配体受体激活剂(RANKL)的表达,促进骨质破坏。然而,牙周炎中免疫-骨细胞相互作用的详细机制尚不完全清楚。在此,我们对小鼠牙周病变进行了单细胞 RNA 序列分析,结果表明,中性粒细胞-成骨细胞串联参与了牙周炎诱导的骨质流失。牙周病灶显示出明显的中性粒细胞浸润,硅学分析表明中性粒细胞通过产生细胞因子与成骨细胞相互作用。在牙周中性粒细胞表达的细胞因子中,oncostatin M(OSM)能有效诱导原发性成骨细胞中 RANKL 的表达,而成骨细胞中 OSM 受体的缺失能显著改善牙周炎诱导的骨质流失。表观基因组数据分析确定了成骨细胞中受OSM调控的RANKL增强子区域,缺乏该增强子的小鼠在维持生理骨代谢的同时,牙周骨质流失也有所减少。这些发现揭示了细菌感染期间中性粒细胞在骨调节中的作用,凸显了骨免疫串扰的新机制。
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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
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.
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