Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis.
Chondrocytes and osteoblasts are two primary cell types in the skeletal system that are differentiated from common mesenchymal progenitors. It is believed that osteoblast differentiation is controlled by distinct mechanisms in intramembranous and endochondral ossification. We have found that ectopic canonical Wnt signaling leads to enhanced ossification and suppression of chondrocyte formation. Conversely, genetic inactivation of beta-catenin, an essential component transducing the canonical Wnt signaling, causes ectopic formation of chondrocytes at the expense of osteoblast differentiation during both intramembranous and endochondral ossification. Moreover, inactivation of beta-catenin in mesenchymal progenitor cells in vitro causes chondrocyte differentiation under conditions allowing only osteoblasts to form. Our results demonstrate that beta-catenin is essential in determining whether mesenchymal progenitors will become osteoblasts or chondrocytes regardless of regional locations or ossification mechanisms. Controlling Wnt/beta-catenin signaling is a common molecular mechanism underlying chondrocyte and osteoblast differentiation and specification of intramembranous and endochondral ossification.
Day
Timothy F
TF
Geneti Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Guo
Xizhi
X
Garrett-Beal
Lisa
L
Yang
Yingzi
Y
D000818:Animals; D001846:Bone Development / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D048429:Cell Size; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D020219:Chondrogenesis; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D007763:Lac Operon; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051153:Wnt Proteins; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D036341:Intercellular Signaling Peptides and Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin