bioRxiv· Calledda, F. R., Abbonante, V., Testa, M. F., Tosi, D., Martinelli, C., Diprima, S., Gioia, R., Gianelli, U., Marty, C., Raslova, H., Plo, I., Balestra, D., Pinotti, M., Balduini, A., Malara, A. ·· 1 day agoPickScore55
Fibronectin silencing remodels the fibrotic bone marrow niche
In brief
Researchers developed a chemically modified antisense oligonucleotide, FN ASO, targeting FN1. Systemic delivery in two mouse models of bone marrow fibrosis reduced fibronectin levels and matrix assembly in the marrow, suppressed TGF-beta1-induced activation of mesenchymal stromal cells, and reduced reticulin fiber and collagen deposition. Transcriptomic analysis in the Jak2V617F-driven model showed downregulation of ECM, TGF-beta1, and mesenchymal gene programs, and short-term treatment was well tolerated.
Why it matters
In two myelofibrosis mouse models, systemic FN1 ASO reduced fibronectin matrix and collagen deposition, providing preclinical proof of concept for targeting extracellular matrix.
Source: bioRxiv