Relationship between SPP1 (Osteopontin) and extracellular matrix dynamics: a comprehensive review

Area of Science:

• Biochemistry
• Cell Biology
• Pathology

Background:

• Secreted Phosphoprotein 1 (SPP1), encoding Osteopontin, is a multifunctional ECM glycoprotein and cytokine.
• SPP1's interaction with collagen and ECM components drives pathological remodeling in various diseases.
• A unified mechanistic framework for SPP1's role in disease is currently lacking.

Purpose of the Study:

• To synthesize evidence on SPP1-mediated ECM dysregulation.
• To elucidate SPP1's role as a central pathological hub in diseases.
• Focus on collagen deposition, epithelial-mesenchymal transition (EMT), and fibrosis.

Main Methods:

• Systematic literature review (1990-2025).
• Synthesis of multi-omics data (scRNA-seq, spatial transcriptomics).
• Integration of machine learning and experimental studies (in vivo/in vitro).

Main Results:

• SPP1 acts as a master regulator of pathological ECM dynamics.
• Conserved SPP1+ macrophage-ECM interactions are key drivers.
• The SPP1-collagen axis is implicated in fibrosis and metastasis.

Conclusions:

• Targeting the SPP1-collagen axis may provide unified strategies for fibrosis and metastasis suppression.
• Future research should focus on in vivo validation in osteoarthritis.
• Clinical translation of SPP1-directed therapies is warranted.