Keskeiset käsitteet
BMP signaling is required to maintain the cell fate of auricular chondrocytes by preventing them from undergoing osteogenic differentiation, and disruption of this signaling leads to microtia development through activation of the PKA pathway.
Tiivistelmä
The study investigates the role of BMP signaling in maintaining the identity of auricular chondrocytes and preventing the development of microtia, a congenital disorder characterized by deformed or underdeveloped ears.
Key highlights:
- Prrx1 genetically marks all auricular chondrocytes in adult mice, in contrast to the limited labeling of chondrocytes in growth plates and articular cartilages.
- Ablation of Bmpr1a in Prrx1+ auricular chondrocytes leads to rapid development of microtia, mainly affecting the distal part of the ear.
- The distal part of the auricle displays the strongest activation of BMP-Smad1/5/9 signaling and the weakest regenerative ability of chondrocytes.
- Transcriptome analysis reveals that Bmpr1a deficiency causes a switch from the chondrogenic program to the osteogenic program, accompanied by enhanced protein kinase A (PKA) activation.
- Inhibition of PKA blocks chondrocyte-to-osteoblast transformation and microtia development in Bmpr1a-deficient mice.
- Analysis of human microtia samples shows enriched gene expression in the PKA pathway and chondrocyte-to-osteoblast transformation process.
The study suggests that BMP signaling is required to maintain the cell fate of auricular chondrocytes by suppressing osteogenic differentiation, and disruption of this signaling leads to microtia development through activation of the PKA pathway.
Tilastot
BMP-Smad1/5/9 signaling is more active at the distal part than at the proximal or middle part of the auricle.
Ablation of Bmpr1a in Prrx1+ auricular chondrocytes leads to a decrease in the thickness of the cartilage and a great reduction in the size of chondrocytes.
Transcriptome analysis shows that Bmpr1a deficiency causes upregulation of genes in inflammation, stemness, cell cycle, mesenchymal cell development, and PKA signaling, and downregulation of genes in chondrocyte differentiation, ECM, and cartilage development.
Bmpr1a deficiency leads to increased expression of osteoblast markers Col1α1, ALP, Runx2, and osteocalcin in auricular chondrocytes.
Lainaukset
"BMP signaling is required to maintain the cell fate of auricular chondrocytes by suppressing osteogenic differentiation, and disruption of this signaling leads to microtia development through activation of the PKA pathway."
"Transcriptome analysis reveals that Bmpr1a deficiency causes a switch from the chondrogenic program to the osteogenic program, accompanied by enhanced protein kinase A (PKA) activation."
"Analysis of human microtia samples shows enriched gene expression in the PKA pathway and chondrocyte-to-osteoblast transformation process."