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This study demonstrates that the infrapatellar fat pad (IFP), an adipose tissue depot within the knee joint, releases significantly more extracellular vesicles (EVs) than subcutaneous fat. These IFP-derived EVs induce a pro-angiogenic response in articular chondrocytes by increasing VEGFA expression 1.6-fold and decreasing BMP4 expression 2.4-fold, while activating key signaling pathways including VEGF/eNOS/ERK. This molecular switch mirrors the angiogenic mechanisms that drive chondrosarcoma, a highly vascularized and treatment-resistant cartilage cancer.
Why it matters
The findings identify a potential local mechanism by which adipose tissue in the knee joint may contribute to blood vessel formation in cartilage tumors. Understanding this pathway could inform new therapeutic strategies for chondrosarcoma, which is notoriously resistant to chemotherapy, and may also have implications for other joint pathologies involving abnormal blood vessel growth.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Chondrosarcoma is a hyper-vascularised, chemoresistant cartilage malignancy driven by VEGF-centred angiogenesis, and local adipose depots are increasingly recognised as paracrine drivers of tumour angiogenesis via adipokines and extracellular vesicles (EVs). The infrapatellar fat pad (IFP), an inflammatory adipose depot within the articular joint in direct cartilage contact, is a key local source of adipose-derived EVs, and thus a candidate driver of angiogenesis in chondrosarcoma. The aim of this study was to determine whether the IFP is a productive source of EVs, and whether IFP-derived EVs induce angiogenesis in articular chondrocytes. The IFP released significantly more EVs than subcutaneous fat (n = 8 per depot; p = 0.027). Treating primary human articular chondrocytes with IFP EVs for 24 h upregulated VEGFA (+1.6-fold, p = 0.036) and downregulated BMP4 (-2.4-fold, p = 0.011), engaging the VEGF/eNOS/ERK axis that drives chondrosarcoma angiogenesis. Re-analysis of a previously published phospho-kinase dataset from the same donor EVs, corroborated by a pooled donor-group analysis (n = 3), supported activation of eNOS, ERK1/2, PLC-{gamma}1 and HSP27. These findings identify the IFP as a dominant source of EVs within the articular joint, which can induce a pro-angiogenic, VEGF-axis switch in articular cartilage cells, supporting a signalling model relevant to chondrosarcoma angiogenesis.