单细胞转录组测序技术在骨质疏松症研究中的应用与进展  

Applications and advances of single-cell transcriptome sequencing technology in osteoporosis research

作　　者：孙成涛[1,2] 孙广江 戚晓楠[3] 程茗 姚啸生 Sun Chengtao;Sun Guangjiang;Qi Xiaonan;Cheng Ming;Yao Xiaosheng(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning Province,China;First Department of Orthopedics and Traumatology,Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110034,Liaoning Province,China;First Department of Orthopedics and Traumatology,Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning Province,China;Fourth People’s Hospital of Shenyang,China Medical University,Shenyang 110031,Liaoning Province,China)

机构地区：[1]辽宁中医药大学,辽宁省沈阳市110847 [2]辽宁中医药大学附属第二医院骨伤一科,辽宁省沈阳市110034 [3]辽宁中医药大学附属医院骨伤一科,辽宁省沈阳市110032 [4]中国医科大学沈阳市第四人民医院,辽宁省沈阳市110031

出　　处：《中国组织工程研究》2025年第13期2812-2821,共10页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金青年科学基金项目(82305275),项目负责人:戚晓楠;辽宁省自然基金资助计划面上项目(2022-MS-284),项目负责人:孙广江;辽宁省科学技术计划医工交叉联合基金(2022-YGJC-79),项目负责人:戚晓楠。

摘　　要：背景:骨质疏松导致的脆性骨折发病率逐年上升,亟需探索其病理生理、潜在生物标志物、治疗靶点及有效药物。骨微环境中存在多种细胞,对骨代谢的维持至关重要。近几年,单细胞RNA测序(scRNA-seq)技术被开发用于表征单个细胞的转录组,并逐步应用到骨质疏松症防治的研究。目的:综述单细胞转录组测序技术在骨质疏松症研究中的应用与进展。方法:由第一作者使用计算机检索Web of Science,PubMed和中国知网数据库中2009-2023年出版的文献,英文检索词为:“single-cell RNA sequencing,bone marrow derived stromal cells,osteoblasts,osteocytes,osteoclasts,immune cells,Bone marrow vascular endothelial cells”;中文检索词为:“单细胞转录组测序,骨髓间充质干细胞,成骨细胞,骨细胞,破骨细胞,免疫细胞,骨髓血管内皮细胞”;通过阅读筛选相关文献,最终纳入89篇文献进行综述分析。结果与结论:①单细胞转录组测序技术能够深入了解细胞发育、增殖、分化的轨迹及其调控机制。②影响骨密度的候选基因主要富集在骨髓间充质干细胞亚群,其中Sox9是关键的转录因子。③成骨细胞不同亚群中差异表达Runx2控制骨髓间充质干细胞向成骨细胞方向分化。④破骨细胞分化过程中RAB38与组蛋白修饰和转录调控动态变化有关。⑤单细胞层面研究证实,骨微环境中存在多种细胞间通讯,破骨细胞可能通过CD160-TNFRSF14配体-受体结合进行细胞间通讯;中性粒/单核细胞与成骨细胞间可能通过RESISTIN通路进行交互;浆样树突状细胞与成骨细胞系通过表皮生长因子通路进行交流;均可以为靶点预测和药物研发提供方向。⑥新的骨髓毛细血管内皮细胞亚群,称为S型内皮细胞,完全起源于骨骺次级骨化中心,甚至比H型血管更具有可塑性。⑦文章从细胞角度总结单细胞转录组测序技术在表征不同骨组织细胞的分化命运和分化轨迹、识�BACKGROUND:The incidence of fragility fractures caused by osteoporosis is increasing year by year,and it is urgent to explore its pathophysiology,potential biomarkers,therapeutic targets and effective drugs.There are multiple cells in the bone microenvironment,which are crucial for maintaining bone metabolism.In recent years,single-cell RNA sequencing technology has been developed to characterize the transcriptome of single cells,and has been gradually applied to the study of osteoporosis prevention and treatment.OBJECTIVE:To review the application and progress of single-cell transcriptome sequencing technology in osteoporosis research.METHODS:The first author used a computer search of Web of Science,PubMed database,and CNKI from 2009 to 2023.Chinese and English search terms were“single-cell RNA sequencing,bone marrow derived stromal cells,osteoblasts,osteocytes,osteoclasts,immune cells,bone marrow vascular endothelial cells.”Through reading and screening of relevant literature,89 articles were finally included in the review analysis.RESULTS AND CONCLUSION:(1)Single-cell transcriptome sequencing technology can gain an in-depth understanding of the trajectory and regulatory mechanism of cell development,proliferation,differentiation.(2)Candidate genes affecting bone mineral density are mainly concentrated in bone marrow mesenchymal stem cell subpopulation,in which Sox9 is a key transcription factor.(3)The differential expression of Runx2 in different subsets of osteoblasts controls the differentiation of bone marrow mesenchymal stem cells into osteoblasts.(4)RAB38 is related to histone modification and transcriptional regulation during osteoclast differentiation.(5)Studies at the single-cell level have confirmed that there are many kinds of intercellular communication in the bone microenvironment,and osteoclast may conduct intercellular communication through CD160-TNFRSF14 ligand-receptor binding.The neutrocyte/monocyte may interact with osteoblasts through the RESISTIN pathway.Plasma dendritic cells communica

关 键 词：单细胞转录组测序 骨质疏松 骨代谢 骨髓间充质干细胞 骨细胞 破骨细胞 骨免疫学 骨髓血管内皮细胞 

分 类 号：R452[医药卫生—治疗学] R363[医药卫生—临床医学] R364