Chinese Journal of Tissue Engineering Research ›› 2025, Vol. 29 ›› Issue (13): 2812-2821.doi: 10.12307/2025.034

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

Sun Chengtao1, 2 , Sun Guangjiang3 , Qi Xiaonan3 , Cheng Ming4 , Yao Xiaosheng3   

  1. 1Liaoning University of Traditional Chinese Medicine, Shenyang 110847, Liaoning Province, China; 2First Department of Orthopedics and Traumatology, Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110034, Liaoning Province, China; 3First Department of Orthopedics and Traumatology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, Liaoning Province, China; 4Fourth People’s Hospital of Shenyang, China Medical University, Shenyang 110031, Liaoning Province, China
  • Received:2024-01-02 Accepted:2024-02-24 Online:2025-05-08 Published:2024-09-12
  • Contact: Yao Xiaosheng, PhD, Doctoral supervisor, Chief physician, First Department of Orthopedics and Traumatology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, Liaoning Province, China
  • About author:Sun Chengtao, Doctoral candidate, Attending physician, 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
  • Supported by:
    National Natural Science Foundation of China for Young Scientists, No. 82305275 (to QXN); General Project of Natural Science Foundation of Liaoning Province, No. 2022-MS-284 (to SGJ); Science and Technology Plan Medical Industry Cross Joint Fund of Liaoning Province, No. 2022-YGJC-79 (to QXN)

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. 

Key words: single-cell transcriptome sequencing, osteoporosis, bone metabolism, bone marrow mesenchymal stem cell, osteocyte, osteoclast, bone immunology, bone marrow vascular endothelial cell

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