Decoding and Targeting IGF1 in Osteoarthritis: From Molecular Mechanisms to Disease Modification
Description: Osteoarthritis (OA) is the most prevalent joint disease and a leading cause of pain and disability, for which disease-modifying therapies remain unavailable. My PhD research identified insulin-like growth factor 1 (IGF1) as critical player in the detrimental effects triggered by Wnt signaling in the joint. Yet, the molecular mechanisms by which IGF1 damages the joint are unknown. This project will define the role of different IGF1 receptors, protein isoforms and derived peptides herein. Furthermore, while my previous work established IGF1’s detrimental role in posttraumatic OA, its involvement in aging-associated OA remains unclear. Understanding this is relevant given the prevalence of OA among older adults, whose disease mechanisms may differ from those in younger people post-injury. This project will remedy this knowledge gap by examining age-related changes in IGF1 and analysing the impact of aging in cartilage-specific Igf1-deficient mice. I will also study IGF1 biology in naked-mole rats, a unique model of healthy aging. Finally, I aim to translate my previous insights into effective IGF1-based therapeutic approaches for OA. Preliminary data show that IGF binding protein 4 (IGFBP4) attenuates IGF1’s harmful effects in chondrocytes. I will evaluate IGFBP4’s therapeutic potential in cartilage explants and in a posttraumatic OA mouse model. My study will bridge crucial knowledge gaps paving the way for innovative strategies to halt OA.
Funder: Fonds Wetenschappelijk Onderzoek
Funding type: fellowship
Funder scheme: FWO junior postdoctoral fellowship
Start date: 2026-10-01
End date: 2029-09-30
Investigators: Ana Escribano Núñez, Rik Lories
Institution: KULeuven
Funded outputs count: 0
Funder award ID: 1288827N
OpenAlex ID: G3734777486