Using a Signalling Pathway Impact Analysis approach to understand signalling pathway perturbations this study demonstrates PI3K- and HIF1-signalling to be associated with both de- and redifferentiation; both native tendon and cartilage show activation of reference pathways for rheumatoid arthritis and systemic lupus erythematosus, whilst 3D cultures were both activated for chemokine signalling. This evidence concerns the gene HIF1A and rheumatoid arthritis.