Interestingly, deletion of the TGFβ receptor type II gene, a component of the TGFβ/SMAD3 signaling system which represses chondrocyte hypertrophic differentiation required for maintaining articular cartilage (Yang et al., 2001), leads to a progressive osteoarthritis-like phenotype in mice (Shen et al., 2013), again illustrating disease causation by both CSPG alteration and major signaling pathways. Here, TGFB1 is linked to osteoarthritis.