Federal Grant Award Summary

The National Institute on Aging (NIA) awarded a Project Grant of $2,265,261 to the University of North Carolina at Chapel Hill, effective July 15, 2026, through June 30, 2030, under the Aging Research program (CFDA 93.866). This project investigates the fundamental cellular mechanisms by which α5β1 integrin signaling contributes to osteoarthritis (OA) progression. The research focuses on how fibronectin fragments activate the α5β1 integrin receptor, triggering a pathological signaling cascade that produces pro-inflammatory mediators and progressive matrix destruction. The project employs a novel mechanistic approach centered on redoxosome-mediated, spatially compartmentalized signaling pathways and utilizes purified bioactive fibronectin fragments (FN7-10) as a model system to define gene expression changes and signaling pathways relevant to OA pathology.

The deliverables include identification of basic cellular mechanisms underlying OA progression, discovery of new therapeutic targets for selectively modulating pathologic integrin signaling while preserving physiologic responses, and generation of mechanistic insights applicable to other OA mediators including cytokine-driven pathways. Through RNAseq analysis and transcriptional profiling, the research will establish correlations between FN7-10-induced gene expression changes and genes differentially expressed in human OA cartilage, thereby advancing basic knowledge needed to develop novel disease-modifying treatments for osteoarthritis.