Modeling the genetic and mechanical interplay in osteoarthritis: from in vitro systems to mechanistic insights

Bloks, N.G.C. (2025)

Doctoral Thesis

Osteoarthritis (OA) is a multi-factorial degenerative disease of joint tissues in which the etio-pathophysiology revolves around the interplay between genetic and environmental risk factors. In current years, several robust genetic studies have elucidated etiopathophysiological pathways. The focus of this thesis was to close the gap between pathway identification and in-depth insight into underlying mechanisms of action, by applying functional follow-up studies. Hereto sustainable 3D in vitro organoid models of articular cartilage were set up, using both primary articular chondrocyte (hPACs) and human induced pluripotent stem cells (hiPSCs). Moreover, to accommodate the exploration of both genetic and OA-relevant environmental perturbations in interaction, hyper-physiologic mechanical loading was incorporated into the models. Multi-modal -omics were used as readouts that facilitated insight into molecular pathophysiological processes involved in OA.

• Osteoarthritis
• Cartilage Organoids
• Multi-omics
• DNA Methylation
• Mechanical Loading

• All authors: Bloks, N.G.C.
• Supervisor: Meulenbelt, I.
• Co-supervisor: Ramos, Y.F.M.
• Committee: Heijmans, B.T.; Lories, R.; Osch, G.J.V.M. van; Welting, T.J.M.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2025-10-22
• ISBN (print): 9789465227320
• Sponsorship: Nederlandse Vereniging voor Matrix Biologie, Medical Delta