Article Information
- PDF (611 kb)
- Full Text with Thumbnail Figures
- Full Text with Large Figures
- Supplemental Data
- Cited by in Scopus (30)
PubMed
Related Articles
- Wnt/β-Catenin Signaling in Mesenchymal Progenitors Controls ...Wnt/β-Catenin Signaling in Mesenchymal Progenitors Controls Osteoblast and Chondrocyte Differentiation during Vertebrate Skeletogenesis
Developmental Cell, Volume 8, Issue 5, 1 May 2005, Pages 739-750
Timothy F. Day, Xizhi Guo, Lisa Garrett-Beal and Yingzi Yang
SummaryChondrocytes 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 , 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 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.
Summary | Full Text | PDF (1024 kb) - Matrix remodeling during endochondral ossificationMatrix remodeling during endochondral ossification
Trends in Cell Biology, Volume 14, Issue 2, 1 February 2004, Pages 86-93
Nathalie Ortega, Danielle J Behonick and Zena Werb
AbstractEndochondral ossification, the process by which most of the skeleton is formed, is a powerful system for studying various aspects of the biological response to degraded extracellular matrix (ECM). In addition, the dependence of endochondral ossification upon neovascularization and continuous ECM remodeling provides a good model for studying the role of the matrix metalloproteases (MMPs) not only as simple effectors of ECM degradation but also as regulators of active signal-inducers for the initiation of endochondral ossification. The daunting task of elucidating their specific role during endochondral ossification has been facilitated by the development of mice deficient for various members of this family. Here, we discuss the ECM and its remodeling as one level of molecular regulation for the process of endochondral ossification, with special attention to the MMPs.
Abstract | Full Text | PDF (507 kb) - Transcriptional mechanisms in osteoblast differentiation and...Transcriptional mechanisms in osteoblast differentiation and bone formation
Trends in Genetics, Volume 19, Issue 8, 1 August 2003, Pages 458-466
Kazuhisa Nakashima and Benoit de Crombrugghe
AbstractOsteoblasts, the cells responsible for bone formation, differentiate from mesenchymal cells. Here, we discuss transcription factors that are involved in regulating the multistep molecular pathway of osteoblast differentiation. Runx2 and Osx, a newly identified zinc-finger-containing protein, are transcription factors that are expressed selectively and at high levels in osteoblasts. Null mutations of either leads to a complete absence of bone in mice. Runx2 plus its companion subunit Cbfβ are needed for an early step in this pathway, whereas Osx is required for a subsequent step, namely the differentiation of preosteoblasts into fully functioning osteoblasts. The finding that -null cells acquire a chondrocyte phenotype implies that Osx is a negative regulator of and of the chondrocyte phenotype. This leads to the hypothesis that Osx might have a role in the segregation of osteoblasts from osteochondroprogenitors. We also discuss recent progress in studies of other transcription factors that affect skeletal patterning and development.
Abstract | Full Text | PDF (1306 kb) - …more
Copyright © 2005 Elsevier Ltd. All rights reserved.
Current Biology, Volume 15, Issue 7, 667-671, 12 April 2005
doi:10.1016/j.cub.2005.02.050
Article
Defective Skeletogenesis with Kidney Stone Formation in Dwarf Zebrafish Mutant for trpm7
Michael R. Elizondo1, 4, Brigitte L. Arduini2, Jennifer Paulsen3, Erin L. MacDonald1, Jaime L. Sabel3, Paul D. Henion2, 
, 
, Robert A. Cornell3, , and David M. Parichy1, 4, ,
1 Section of Integrative Biology and Section of Molecular, Cell and Developmental Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, 1 University Station C0930, Austin, Texas 78712
2 Center for Molecular Neurobiology and Department of Neuroscience, Ohio State University, 105 Rightmire Hall, 1060 Carmack Rd., Columbus, Ohio 43210
3 Department of Anatomy and Cell Biology, Roy and Lucille Carver College of Medicine, 1-532 Bowen Science Building, University of Iowa, Iowa City, Iowa 52242
Ph: (614) 292-5111; F: (614) 292-5379 [P.H.]Ph: (319) 335-8909; F: (319) 335-7198 [R.C.]Ph: (206) 543-1620; F: (206) 543-3041 [D.P.]4 Present address: Department of Biology, University of Washington, Box 351800, Seattle, Washington 98195.
Summary
Development of the adult form requires coordinated growth and patterning of multiple traits in response to local gene activity as well as to global endocrine and physiological effectors. An excellent example of such coordination is the skeleton. Skeletal development depends on the differentiation and morphogenesis of multiple cell types to generate elements with distinct forms and functions throughout the body [1,2,3]. We show that zebrafish touchtone/nutria mutants exhibit severe growth retardation and gross alterations in skeletal development in addition to embryonic melanophore and touch-response defects [4,5]. These alterations include accelerated endochondral ossification but delayed intramembranous ossification, as well as skeletal deformities. We show that the touchtone/nutria phenotype results from mutations in trpm7, which encodes a transient receptor potential (TRP) family member that functions as both a cation channel and kinase. We find trpm7 expression in the mesonephric kidney and show that mutants develop kidney stones, indicating renal dysfunction. These results identify a requirement for trpm7 in growth and skeletogenesis and highlight the potential of forward genetic approaches to uncover physiological mechanisms contributing to the development of adult form.
