Characterizing gene expression in an  in vitro biomechanical strain model of joint health [version 2; peer review: 1 approved, 1 not approved]

Background: Both genetic and environmental factors appear to contribute to joint health and disease. For example, pathological levels of biomechanical stress on joints play a notable role in initiation and progression of osteoarthritis (OA), a common chronic degenerative joint disease affecting articular cartilage and underlying bone. Population-level gene expression studies of cartilage cells experiencing biomechanical stress may uncover gene-by-environment interactions relevant to human joint health. Methods: To build a foundation for population-level gene expression studies in cartilage, 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. Results: We identified patterns of gene regulation that differ between strain-treated and control iPSC-chondrocytes. Differentially expressed genes between strain and control conditions are enriched for gene sets relevant to joint health and OA. Furthermore, even in this small sample, we found several genes that exhibit inter-individual expression differences in response to mechanical strain, including genes previously implicated in OA. Conclusions: 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 joint health.