CCN2 and osteoarthritis: Human mutations in SMAD3 or deletion of SMAD3 in mice is associated with increased risk of osteoarthritis.43 47 48 Although we did not examine SMAD3 phosphorylation directly, SMAD2 was phosphorylated both in vitro after stimulation with TGFβ or CTGF and, somewhat paradoxically, in vivo after CTGF deletion.