Primary mouse embryonic fibroblasts: A model of mesenchymal cartilage formation

Christopher J. Lengner, Christoph Lepper, Andre J. Van Wijnen, Janet L. Stein, Gary S. Stein, Jane B. Lian

Research output: Contribution to journalArticle

65 Scopus citations

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 prb-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.

Original languageEnglish (US)
Pages (from-to)327-333
Number of pages7
JournalJournal of Cellular Physiology
Volume200
Issue number3
DOIs
StatePublished - Sep 1 2004

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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    Lengner, C. J., Lepper, C., Van Wijnen, A. J., Stein, J. L., Stein, G. S., & Lian, J. B. (2004). Primary mouse embryonic fibroblasts: A model of mesenchymal cartilage formation. Journal of Cellular Physiology, 200(3), 327-333. https://doi.org/10.1002/jcp.20118