[PDF][PDF] Wnt/β-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis

TF Day, X Guo, L Garrett-Beal, Y Yang - Developmental cell, 2005 - cell.com
TF Day, X Guo, L Garrett-Beal, Y Yang
Developmental cell, 2005cell.com
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 β-
catenin, an essential component transducing the canonical Wnt signaling, causes ectopic …
Summary
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 β-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 β-catenin in mesenchymal progenitor cells in vitro causes chondrocyte differentiation under conditions allowing only osteoblasts to form. Our results demonstrate that β-catenin is essential in determining whether mesenchymal progenitors will become osteoblasts or chondrocytes regardless of regional locations or ossification mechanisms. Controlling Wnt/β-catenin signaling is a common molecular mechanism underlying chondrocyte and osteoblast differentiation and specification of intramembranous and endochondral ossification.
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