Characterizing gene expression responses to biomechanical strain in an in vitro model of osteoarthritis

Abstract

Osteoarthritis (OA) is a common chronic degenerative joint disease affecting articular cartilage and underlying bone. Both genetic and environmental factors appear to contribute to the development of this disease. Specifically, pathological levels of biomechanical stress on joints play a notable role in disease initiation and progression. Population-level gene expression studies of cartilage cells experiencing biomechanical stress may uncover gene-by-environment interactions relevant to OA and human joint health. To build a foundation for such studies, we applied differentiation protocols to develop an in vitro system of chondrogenic cell lines (iPSC-chondrocytes). We characterized gene regulatory responses of three human iPSC-chondrocyte lines to cyclic tensile strain treatment. We measured the contribution of biological and technical factors to gene expression variation in this system and, even in this small sample, found several genes that exhibit inter-individual expression differences in response to mechanical strain, including genes previously implicated in OA. Expanding this system to include iPSC-chondrocytes from a larger number of individuals will allow us to characterize and better understand gene-by-environment interactions related to OA and joint health.