Lack of periostin in mice leads to suppression of Notch1 signaling, ectopic expression of pleiotrophin, overexpression of Dlk1, and subsequent calcification of the aortic valve.
Periostin is a key regulator of outflow tract endocardial cushion mesenchymal cell fate, and its absence leads to calcific aortic valve disease via suppression of Notch1 signaling.
The Postn gene encodes protein periostin. During embryonic development, it is highly expressed in the outflow tract (OFT) endocardial cushions of the developing heart, which give rise to several structures of the mature heart including the aortic valve. Periostin was previously implicated in osteoblast differentiation, cancer metastasis, and tooth and bone development, but its role in cardiac OFT development is unclear. To elucidate the role that periostin plays in the developing heart we analyzed cardiac OFT phenotype in mice after deletion of the Postn gene. We found that lack of periostin in the embryonic OFT leads to ectopic expression of the proosteogenic growth factor pleiotrophin (Ptn) and overexpression of delta-like 1 homolog (Dlk1), a negative regulator of Notch1, in the distal (prevalvular) cushions of the OFT. This resulted in suppression of Notch1 signaling, strong induction of the central transcriptional regulator of osteoblast cell fate Runx2, upregulation of osteopontin and osteocalcin expression, and subsequent calcification of the aortic valve. Our data suggest that periostin represses a default osteogenic program in the OFT cushion mesenchyme and promotes differentiation along a fibrogenic lineage. Lack of periostin causes derepression of the osteogenic potential of OFT mesenchymal cells, calcium deposition, and calcific aortic valve disease. These results establish periostin as a key regulator of OFT endocardial cushion mesenchymal cell fate during embryonic development.
Tkatchenko et al. (Wed,) conducted a other in Calcific aortic valve disease (n=258). Postn gene deletion (Lack of periostin) vs. Wild-type mice was evaluated on Development of calcific aortic valve disease and alterations in Notch1 signaling. Lack of periostin in mice leads to suppression of Notch1 signaling, ectopic expression of pleiotrophin, overexpression of Dlk1, and subsequent calcification of the aortic valve.