In agreement with this idea, ex-vivo treatment of OI fibroblasts with losartan had no effect on SMAD2 phosphorylation nor did losartan affect genes associated with the renin-angiotensin pathway and only minimal effects on genes associated with the TGFβ family, their modulators, or genes directly downstream of TGFβ or the MAPK pathway. Here, REN is linked to osteogenesis imperfecta.