ArticleMolecular biology reports2026
TNF-α orchestrates ADAM metallopeptidase with thrombospondin type 1 motif 2 upregulation and extracellular matrix remodeling through multimodal signaling in osteosarcoma cells.
Article in Molecular biology reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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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.
- Current Advances in the Physiological Roles and Disease-Associated Mechanisms of ADAMTS16.International journal of molecular sciences · 2026Review
- Comparative Effects of Thymoquinone, Tranexamic Acid, and Porcine Dermal Collagen on Seroma Formation and Tissue Remodeling After Mastectomy in a Rat Model.Medicina (Kaunas, Lithuania) · 2026Article
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Authors and funding
4 authors.
Funding
Abstract
backgroundADAMTS-2 is a key extracellular matrix (ECM) remodeling enzyme increasingly implicated in osteosarcoma biology. Although ADAMTS-2 is known to participate in collagen processing and ECM turnover, the upstream inflammatory cues and transcriptional mechanisms regulating its expression in osteosarcoma remain unclear. Tumor necrosis factor-α (TNF-α), a dominant pro-inflammatory cytokine within the osteosarcoma microenvironment, represents a strong candidate regulator due to its ability to activate several pathways. This study aimed to elucidate the TNF-α-ADAMTS-2 regulatory axis at mechanistic levels. METHODS AND
resultsGene expression profiling revealed that ADAMTS-2 is significantly upregulated in osteosarcoma tissues compared with normal bone and is associated with ECM disassembly and collagen fibril organization pathways. Functional assays in Saos-2 cells demonstrated that TNF-α stimulation markedly increased ADAMTS-2 mRNA (~ 17-fold) and protein levels (~ twofold). Promoter activity assays showed strong TNF-α-mediated activation, with the highest induction in the - 180/ + 112 region. Pharmacological inhibition experiments revealed that MEK, PI3K, JNK, and NF-κB pathways are all required for TNF-α-induced ADAMTS-2 transcription. In silico motif analysis identified STAT3 and NF-κB binding elements within the promoter, and electrophoretic mobility shift assays supported the interaction of these transcription factors with specific promoter regions.
conclusionsThis study provides the first mechanistic evidence that TNF-α regulates ADAMTS-2 expression through the coordinated activation of multiple signaling pathways and the engagement of STAT3 and NF-κB transcription factors at the promoter. These findings uncover a previously uncharacterized inflammatory regulatory axis linking TNF-α signaling to ECM remodeling and highlight ADAMTS-2 as a potential mediator of osteosarcoma progression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.