大鼠颞下颌关节骨关节炎中髁突软骨与骨髓的单细胞转录组分析

doi:10.19438/j.cjoms.2023.04.003

中国口腔颌面外科杂志 ›› 2023, Vol. 21 ›› Issue (4): 332-339.doi: 10.19438/j.cjoms.2023.04.003

大鼠颞下颌关节骨关节炎中髁突软骨与骨髓的单细胞转录组分析

余也可^1,2,3, 丁若仪^1,3, 孙家莉^1,3, 张志愿^2,3,*, 何冬梅^1,3,*

1.上海交通大学医学院附属第九人民医院口腔外科,2.口腔颌面-头颈肿瘤科,上海 200011;
3.上海交通大学口腔医学院,国家口腔医学中心,国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室,上海市口腔医学研究所,中国医学科学院口腔颌面再生医学创新单元,上海 200011

收稿日期:2023-02-16 修回日期:2023-03-16 出版日期:2023-07-20 发布日期:2023-08-16
通讯作者: 张志愿,E-mail：zhzhy0502@163.com; 何冬梅,E-mail：Lucyhe119@163.com。^*共同通信作者
作者简介:余也可（1997-）,女,在读硕士研究生,E-mail：alokyu@163.com
基金资助:
国家重点研发计划（2020YFC2002800）; 国家自然科学基金（32071313, 82270996）; 中国医学科学院医学与健康科技创新工程项目（2019-I2M-5-037）

Single-cell transcription atlas for mandibular condyle cartilage and subchondral bone marrow in rat temporomandibular joint osteoarthritis

YU Ye-ke^1,2,3, DING Ruo-yi^1,3, SUN Jia-li^1,3, ZHANG Zhi-yuan^2,3, HE Dong-mei^1,3

1. Department of Oral Surgery, 2. Department of Oromaxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. Shanghai 200011;
3. College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology; Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences. Shanghai 200011, China

Received:2023-02-16 Revised:2023-03-16 Online:2023-07-20 Published:2023-08-16

摘要/Abstract

摘要： 目的：以单细胞分辨率解析髁突软骨及骨髓的细胞组成与功能,及其在异常咬合应力下导致的颞下颌关节骨关节炎（temporomandibular joint osteoarthritis,TMJOA）中的变化。方法：构建大鼠单侧反（unilateral anterior crossbite,UAC）诱导的TMJOA模型。分离提取正常与UAC大鼠髁突软骨与骨髓细胞,进行单细胞转录组测序。通过质控、降维、分群、标志物分析,区分髁突细胞亚群组成。通过差异表达基因功能富集分析,明确细胞亚群功能变化。通过拟时序分析,探索细胞功能分化轨迹。通过细胞通讯预测,分析细胞间相互作用变化。结果：大鼠髁突的软骨细胞与骨髓免疫细胞分为9个亚群,在UAC中,软骨细胞减少、骨髓免疫细胞增加。髁突软骨细胞由6个功能群组成,其中具有前体细胞特征的D、F功能群可向其他细胞群分化。UAC中,软骨细胞外基质分泌功能下降、衰老与炎症通路激活、细胞间相互作用下降;骨髓中,中性粒细胞趋化、脱颗粒功能上调,单核-巨噬细胞吞噬功能激活,活化B细胞增加。结论：髁突软骨中存在不同软骨细胞亚群,异常咬合导致其数量变化、功能失调,同时引起骨髓免疫细胞功能激活。

关键词: 颞下颌关节骨关节炎, 异常咬合, 单细胞转录组测序, 前体细胞, 免疫细胞, 大鼠

Abstract: PURPOSE: To establish the single-cell transcriptome atlas for rat condyle osteochondral tissue and bone marrow both in normal and temporomandibular joint osteoarthritis (TMJOA) condition. METHODS: Rat unilateral anterior crossbite(UAC) model was built to induce TMJOA. Osteochondral cells and bone marrow immune cells were extracted for single-cell RNA sequencing. Quality control, dimension reducing, clustering and marker gene detection were used to depict cell subclusters. Differential gene expression analysis and functional enrichment were utilized to demonstrate cell cluster functions and their changes under UAC. Pseudo-time analysis was applied for cell development trajectory, while cell communication prediction was used to show alternations in the interaction among cell clusters. RESULTS: There were 9 cell clusters in rat condyle, containing osteochondral cells and bone marrow immune cells. Under UAC, the number of osteochondrocytes decreased whereas immune cells accumulated. Condyle cartilage and bone tissue contained 6 functional groups of cells. Among them, D and F group maintained progenitor characteristics and possessed the ability to develop into other groups. In UAC condition, osteochondrocytes witnessed impaired extracellular matrix organization, activated senescent or inflammatory pathways, and diminished cell-cell interaction. Meanwhile, in the bone marrow, neutrophils showed enhanced chemotaxis and degranulation, mononuclear-phagocytes displayed increased phagosomes, activated B cells were also recruited. CONCLUSIONS: There are progenitor cells in condyle cartilage and bone tissue, whose function impaired under UAC. At the same time, immune cells in the bone marrow are activated. Targeted modulation of osteochondral progenitors and immune cells could contribute in alleviation the condyle tissue damage in TMJOA.

Key words: Temporomandibular joint osteoarthritis, Malocclusion, Single-cell transcriptome, Progenitor cells, Immune cells, Rat

中图分类号:

R782.6

余也可, 丁若仪, 孙家莉, 张志愿, 何冬梅. 大鼠颞下颌关节骨关节炎中髁突软骨与骨髓的单细胞转录组分析[J]. 中国口腔颌面外科杂志, 2023, 21(4): 332-339.

YU Ye-ke, DING Ruo-yi, SUN Jia-li, ZHANG Zhi-yuan, HE Dong-mei. Single-cell transcription atlas for mandibular condyle cartilage and subchondral bone marrow in rat temporomandibular joint osteoarthritis[J]. China J Oral Maxillofac Surg, 2023, 21(4): 332-339.

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大鼠颞下颌关节骨关节炎中髁突软骨与骨髓的单细胞转录组分析

Single-cell transcription atlas for mandibular condyle cartilage and subchondral bone marrow in rat temporomandibular joint osteoarthritis

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