REVIEW article
Front. Med.
Sec. Pulmonary Medicine
Relationship Between SPP1 (Osteopontin) and Extracellular Matrix Dynamics: A Comprehensive Review
Provisionally accepted
- 1XiangYang Hospital of Traditional Chinese Medicine, Xiangyang, China
- 2Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, China
- 3Shandong Provincial Hospital, Jinan, China
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Background: Secreted Phosphoprotein 1 (SPP1), which encodes Osteopontin, a key member of the SIBLING family, is a multifunctional ECM glycoprotein and cytokine. Its interaction with collagen and other ECM components drives pathological remodeling across multiple diseases, yet a unified mechanistic framework remains elusive. Objective: This review synthesizes current evidence on SPP1-mediated ECM dysregulation, focusing on collagen deposition, epithelial-mesenchymal transition (EMT), and fibrosis, with the goal of elucidating its role as a central pathological hub. Methods: We synthesize the findings from multi-omics analyses (single-cell RNA sequencing, spatial transcriptomics), machine learning, and in vivo/in vitro experimental studies, aiming to elucidate the role of SPP1 (Osteopontin) in the dysregulation of the extracellular matrix (ECM) across various diseases via a systematic literature review (1990–2025). Conclusion: SPP1 is a master regulator of pathological ECM dynamics, driven by conserved SPP1⁺ macrophage-ECM interactions. Targeting the SPP1-collagen axis may offer unified strategies for fibrosis and metastasis suppression. Future work should prioritize in vivo validation in osteoarthritis and clinical translation of SPP1-directed therapies.
Keywords: SPP1, Osteopontin, Extracellular Matrix (ECM), SPP1+ macrophages, Epithelial-mesenchymal transition (EMT)
Received: 07 Sep 2025; Accepted: 28 Oct 2025.
Copyright: © 2025 Liu, Yan and Fan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Rui Fan, fanruialbert@foxmail.com
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