Cripto favors chondrocyte hypertrophy via TGF-β SMAD1/5 signaling during development of osteoarthritis.

ABSTRACT: Chondrocytes in mice developing osteoarthritis (OA) exhibit an aberrant response to the secreted cytokine transforming growth factor (TGF)-β, consisting in a potentiation of intracellular signaling downstream of the transmembrane type I receptor kinase activin receptor-like kinase (ALK)1 against canonical TGF-β receptor ALK5-mediated signaling. Unfortunately, the underlying mechanisms remain elusive. In order to identify novel druggable targets for OA, we aimed to investigate novel molecules regulating the ALK1/ALK5 balance in OA chondrocytes. We performed gene expression analysis of TGF-β signaling modulators in joints from three different mouse models of OA and found an upregulated expression of the TGF-β co-receptor Cripto (Tdgf1), which was validated in murine and human cartilage OA sa

SUBMITTER: Garcia de Vinuesa A 

PROVIDER: S-EPMC9292799 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature