ArticleJournal of translational medicine2025
The integrin α2-osteoclast axis: a key driver of bone destruction and therapeutic target in osteosarcoma.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed.
- Comparative clinical and prognostic significance of integrin αvβ3, αvβ5, and αvβ6 in osteosarcoma.Frontiers in oncology · 2026Article
- Tumor-associated osteoclasts converge on a matrix-sulfation program across human bone tumors.Frontiers in cell and developmental biology · 2026Article
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Authors and funding
7 authors.
Funding
Abstract
backgroundOsteosarcoma is an aggressive bone malignancy with elusive core driving mechanisms. Dysregulated expression of integrin α2 (ITGA2) promotes malignant progression in multiple cancers, yet its role in osteosarcoma and correlation with bone destruction remain poorly understood. This study investigated the potential role of ITGA2 in osteosarcoma progression and therapeutic targeting.
methodsIntegrating bioinformatics analysis and experimental validation, we explored ITGA2 dysregulation and its clinical significance in osteosarcoma. Public databases were analyzed to confirm ITGA2 overexpression. CCK-8 assay, colony formation, Transwell migration/invasion assays, wound healing, and cell transcriptomics were employed to assess ITGA2's impact on tumor proliferation, migration, and invasion. Xenograft mouse models evaluated ITGA2-driven tumor growth and osteolytic damage. WB analyzed ITGA2-mediated modulation of osteoclast differentiation-related molecules (RANKL, MMP9, OPN). ITGA2 knockdown and inhibitor (E7820) intervention were applied, with Western Blot (WB)/ Immunohistochemistry (IHC) validating ITGA2-MMP9 interactions.
resultsClinical cohorts and bioinformatics revealed ITGA2-specific overexpression in osteosarcoma tissues/cells (P < 0.0001), correlating with poor prognosis (HR = 3.392). Pathway analysis linked ITGA2 to bone remodeling and osteoclast differentiation. Functional assays showed that ITGA2 inhibition decreased cell proliferation and migration/invasion by 2-threefold (all P < 0.001), and reduced tumor volume and decreased osteoclast numbers (TRAP staining) in mouse models. Mechanistically, ITGA2 blockade downregulated MMP9 (pro-osteoclast) and upregulated OPN (pro-osteogenesis), indicating its role in exacerbating bone destruction via osteoclast differentiation cascades. ITGA2 emerged as an independent prognostic biomarker.
conclusionThis study uncovered that ITGA2 drives osteosarcoma progression and aggravates osteolysis via the "ITGA2-osteoclast axis", with high expression predicting poor outcomes. Mechanistically, ITGA2 promoted tumor invasion and bone metabolism imbalance by regulating osteoclastogenic signaling, while its targeted inhibition synergistically suppresses tumor growth and restores bone homeostasis, highlighting ITGA2 as a pivotal therapeutic target for osteosarcoma.
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