Effect of knockout on OA disease model.

The first and second column contain the effect of a knockout in the attractor basin. We check whether a knockout (either through the use of a small molecule inhibitor or by a genetic KO) indeed confers protection to OA, indicated as ‘protective’. Sometimes a knockout is seen to aggravate symptoms, indicated as ‘reverse’. Finally, cases where no knockout was found, are marked by ‘absent’. Sometimes indirect support, namely that the protein’s constitutive activation entails hypertrophy, is found. Papers indicating this are referenced after the ‘absent’ tag. For SMAD7, one study found increased Smad7 expression was accompanied by a reduction in osteophyte formation [67]. *In the network model, an insulation of GSK in the destruction complex from cytosolic GSK is assumed. In the case of a knockout this would not hold. Hence a double mutant, with a knockout of both destruction complex (DC) and GSK, constitutes a more appropriate simulation.