Full Papers
Single-cell analysis reveals the role of interleukins in impairing osteogenic differentiation of mesenchymal stem cells and promoting osteoporosis
Z. Zhang1, X. Yang2, C. Wang3, J. He4, Q. Fang5, Y. Zhu6, H. Cai7
- Department of Emergency Trauma Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian; and Department of Emergency Trauma Surgery, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, China.
- Spinal Ward, Fuzong Clinical Medical College of Fujian Medical University, The 900th Hospital of PLA Joint Logistic Support Force, Fuzhou, Fujian, China.
- Department of Emergency Trauma Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian; and Department of Emergency Trauma Surgery, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, China.
- Department of Emergency Trauma Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian; and Department of Emergency Trauma Surgery, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, China.
- Department of Emergency Trauma Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian; and Department of Emergency Trauma Surgery, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, China.
- Department of Emergency Trauma Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian; and Department of Emergency Trauma Surgery, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, China.
- Department of Emergency Trauma Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian; and Department of Emergency Trauma Surgery, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, China. hongrucaihr@163.com
CER19356
Full Papers
Received: 26/09/2025
Accepted : 21/04/2026
In Press: 13/05/2026
Abstract
OBJECTIVES:
Osteoporosis (OP) is a prevalent skeletal disorder characterised by reduced bone mass and microarchitectural deterioration, leading to increased fracture risk and a heavy global health burden. Chronic interleukin (IL)-mediated inflammation is closely linked to bone-remodelling imbalance, yet the molecular mechanisms by which ILs govern MSC fate in the OP microenvironment remain unclear. This study uses single-cell RNA sequencing to dissect the role of ILs in OP occurrence and progression.
METHODS:
Through single-cell transcriptomics, OP and osteoarthritis (OA) samples, from the GSE147287 dataset were analysed. AUCell scoring, functional enrichment, pseudotime trajectory, and cell-cell communication analyses were employed to systematically evaluate how ILs contribute to OP.
RESULTS:
Single-cell transcriptomics revealed that OP samples contained a higher proportion of MSCs with imbalanced differentiation. Osteogenic MSCs in OP exhibited specific activation of IL signalling, significant enrichment of TGF-β and interferon pathways, and specific up-regulation of IL1R1, IL7, IL34, and other IL-related genes. Trajectory analysis showed sustained or increasing expression of these genes in OP. Cell-cell communication analysis revealed selective activation of the IL34-CSF1R axis between osteogenic MSCs and monocytes in OP. Diagnostic analysis further indicated high diagnostic value of IL34 for OP.
CONCLUSIONS:
We uncovered a previously unrecognised mechanism in which aberrant IL signalling in the OP microenvironment suppressed MSC osteogenic differentiation. The IL34-CSF1R axis represented a potential therapeutic target, and IL34 itself could be a new biomarker and target for OP diagnosis and treatment.
