Applications and advances of single-cell transcriptome sequencing technology in osteoporosis research
- VernacularTitle: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
- Author:
Chengtao SUN
1
;
Guangjiang SUN
;
Xiaonan QI
;
Ming CHENG
;
Xiaosheng YAO
Author Information
- Publication Type:Journal Article
- Keywords: single-cell transcriptome sequencing; osteoporosis; bone metabolism; bone marrow mesenchymal stem cell; osteocyte; osteoclast; bone immunology; bone marrow vascular endothelial cell
- From: Chinese Journal of Tissue Engineering Research 2025;29(13):2812-2821
- CountryChina
- Language:Chinese
- Abstract: 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 communicate with osteoblast cell lines through the epidermal growth factor pathway.Both can provide directions for target prediction and drug development.(6) An unrecognized capillary subset is called S-type endothelial cells,which originates entirely from the secondary ossification center of the epiphysis,and is even more malleable than H-type blood vessels.(7) This paper reviews the progress of single-cell transcriptome sequencing in characterizing the differentiation fate and differentiation trajectory of different bone tissue cells,identifying new cell subsets,identifying cell regulatory factors,and clarifying intercellular communication from a cellular perspective,so as to provide cell-level information for exploring the pathogenesis of osteoporosis,screening potential diagnostic markers,predicting therapeutic targets,and exploring the mechanism of drug action.(8) In the future,single-cell sequencing technology will provide more valuable information for changes in the bone microenvironment in the direction of single-cell multiomics (genomics,proteomics,and metabolomics) and other technologies such as spatial transcriptome technology.
