🚨 New Publication Alert! 🚨
Happy to share that our recent study, published in Nature Communications, reveals an exciting discovery in osteoarthritis (OA) research. Our team at KU Leuven with my co-lead Prof. Silvia Monteagudo PharmD, PhD, and first author Ana Escribano Nuñez, has identified IGF1 as a surprising driver of cartilage damage in OA, opening the door to potential new therapies that could slow or even halt disease progression.
📌 What we found: While IGF1 has been classically associated with growth and repair, we discovered that excessive Wnt signaling in osteoarthritis triggers harmful increases in IGF1, accelerating joint degeneration. We used advanced genetic models in mice to demonstrate the direct link between Wnt signaling and IGF1. In these models, the team deleted IGF1 specifically in the cartilage cells, and the results were remarkable. Mice without IGF1 in their joints were protected from cartilage breakdown when Wnt signaling was excessively activated, and even upon surgically inducing joint injury in a mouse model of osteoarthritis. This offers a promising new therapeutic target in OA, a condition that affects over 500 million people worldwide.
📌 A detailed mechanism: To dive deeper in the molecular mechanisms underlying the Wnt-IGF1 link, we used luciferase reporter assays and chromatin immunoprecipitation (ChIP) experiments. These showed that Wnt signaling directly increases IGF1 expression as Wnt transcription factor TCF4 binds to the IGF1 gene promoter. We also found TCF/LEF binding sites in the IGF1 gene promoter, highly conserved across species. Our results indicate that IGF1 is a direct Wnt target gene! This unravels a molecular mechanism for how Wnt signaling leads to increased IGF1 in the joint, driving OA.
🔬 Why this matters: Osteoarthritis currently has no treatments that can alter its course, leaving patients with only symptom relief options. Our findings provide hope for a new approach that could prevent or delay joint replacement surgery.
💡 Next steps: Our work doesn’t stop here! We are advancing this research by developing now pharmacological approaches to block IGF1 in osteoarthritis and exploring the broader implications of the new Wnt-IGF1 link in other Wnt-associated diseases like cancer and fibrosis.
I’m grateful to the entire research team Ana Escribano Nuñez Frederique Cornelis Astrid De Roover Prof. A Sermon Frédéric Cailotto for their outstanding contributions. Let’s continue to work together to understand cartilage biology and define roads towards treatments in osteoarthritis that improve patient outcomes!
Work supported by KU Leuven, UZ Leuven, Research Foundation Flanders - FWO
