AccScience Publishing / OTE / Online First / DOI: 10.36922/OTE025310007
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ORIGINAL RESEARCH ARTICLE

Elucidating the therapeutic mechanisms of Chaenomeles speciosa on osteogenesis imperfecta through integrative multi-omics and computational approaches

Kaihan Zhuang1 ,  Shengjin Yuan1 ,  Henghe Zheng1 ,  Bolin Chen1 ,  Guanghong Wu1 ,  Haoyu Xu1 ,  Jian Wang2*
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1 Department of Clinical Medicine, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
2 Department of Orthopaedics, Division of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
OTE, 025310007 https://doi.org/10.36922/OTE025310007
Received: 1 August 2025 | Revised: 24 September 2025 | Accepted: 6 November 2025 | Published online: 20 November 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Osteogenesis imperfecta (OI) is characterized by severe bone fragility resulting from collagen gene mutations, with limited therapeutic options available. Chaenomeles speciosa exhibits potential in regulating chondrocyte function; however, the mechanism by which it may exert therapeutic effects in OI remains unclear. In this study, single-cell RNA sequencing was employed to analyze the chondrocyte population in Aga2 OI mice. The therapeutic mechanism of C. speciosa was investigated using network pharmacology and molecular docking techniques, and the bone immune microenvironment was evaluated through cell–cell interaction analysis. Results showed that, compared with the wild-type control group, the hypertrophic chondrocyte population was significantly increased in Aga2 OI mice. Network pharmacology identified two bioactive compounds in C. speciosa that targeted 147 OI-related genes. Molecular docking revealed a strong binding affinity between these compounds and proteins involved in the mitogen-activated protein kinase (MAPK) pathway, with binding energies ranging from −8.2 to −9.5 kcal/mol. Impaired communication between chondrocytes and bone immune cells, as well as abnormalities in hypoxia response (p<0.01) and apoptotic pathways (p<0.01) were observed in OI mice. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the MAPK signaling pathway is the primary mechanism by which C. speciosa normalizes the chondrocyte population and restores intercellular signaling pathways. This study elucidates the role of chondrocyte dysfunction in OI pathogenesis, predicts the active components, targets, and pathways of C. speciosa for OI treatment, and provides a basis for further mechanistic research and drug development.

Keywords
Single-cell RNA sequencing
Network pharmacology
Osteogenesis imperfecta
Chaenomeles speciosa
Mitogen-activated protein kinase signal transduction
Funding
None.
Conflict of interest
Jian Wang is the Editor-in-Chief of this journal, but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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