GSBS Student Publications

Title

Primary mouse embryonic fibroblasts: a model of mesenchymal cartilage formation

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cell Biology

Date

7-16-2004

Document Type

Article

Medical Subject Headings

Alkaline Phosphatase; Animals; Bone Morphogenetic Proteins; Cartilage; Cell Communication; Cell Differentiation; Cells, Cultured; Chondrocytes; *Chondrogenesis; Collagen Type II; Collagen Type X; Embryo, Mammalian; Extracellular Matrix; Fibroblasts; Gene Expression; Hedgehog Proteins; Hypertrophy; Mesoderm; Mice; Mice, Inbred C57BL; Osteocalcin; Stem Cells; Time Factors; Trans-Activators; Transcription Factors; *Transforming Growth Factor beta

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Cartilage formation is an intricate process that requires temporal and spatial organization of regulatory factors in order for a mesenchymal progenitor cell to differentiate through the distinct stages of chondrogenesis. Gene function during this process has best been studied by analysis of in vivo cartilage formation in genetically altered mouse models. Mouse embryonic fibroblasts (MEFs) isolated from such mouse models have been widely used for the study of growth control and DNA damage response. Here, we address the potential of MEFs to undergo chondrogenic differentiation. We demonstrate for the first time that MEFs can enter and complete the program of chondrogenic differentiation ex vivo, from undifferentiated progenitor cells to mature, hypertrophic chondrocytes. We show that chondrogenic differentiation can be induced by cell-cell contact or BMP-2 treatment, while in combination, these conditions synergistically enhance chondrocyte differentiation resulting in the formation of 3-dimensional (3-D) cartilaginous tissue ex vivo. Temporal expression profiles of pro-chondrogenic transcription factors Bapx1 and Sox9 and cartilaginous extracellular matrix (ECM) proteins Collagen Type II and X (Coll II and Coll X) demonstrate that the in vivo progression of chondrocyte maturation is recapitulated in the MEF model system. Our findings establish the MEF as a powerful tool for the generation of cartilaginous tissue ex vivo and for the study of gene function during chondrogenesis.

Rights and Permissions

Citation: J Cell Physiol. 2004 Sep;200(3):327-33. Link to article on publisher's site

DOI of Published Version

10.1002/jcp.20118

Related Resources

Link to article in PubMed

Journal Title

Journal of cellular physiology

PubMed ID

15254959