Embryonic stem cell-derived chondrogenic differentiation in vitro: activation by BMP-2 and BMP-4.
Differentiation of mouse embryonic stem (ES) cells via embryoid bodies was established as a suitable model to study development in vitro. Here, we show that differentiation of ES cells in vitro into chondrocytes can be modulated by members of the transforming growth factor-beta family (TGF-beta(1), BMP-2 and -4). ES cell differentiation into chondrocytes was characterized by the appearance of Alcian blue-stained areas and the expression of cartilage-associated genes and proteins. Different stages of cartilage differentiation could be distinguished according to the expression pattern of the transcription factor scleraxis, and the cartilage matrix protein collagen II. The number of Alcian-blue-stained areas decreased slightly after application of TGF-beta(1), whereas BMP-2 or -4 induced chondrogenic differentiation. The inducing effect of BMP-2 was found to be dependent on the time of application, consistent with its role to recruit precursor cells to the chondrogenic fate.
Kramer
J
J
Department of Medical Molecular Biology, Medical University of Lübeck, Ratzeburger Allee 160, D-23538, Lübeck, Germany.
Hegert
C
C
Guan
K
K
Wobus
A M
AM
Müller
P K
PK
Rohwedel
J
J
D053674:Aggrecans; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002356:Cartilage / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology; D016326:Extracellular Matrix Proteins; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins / Q000235:genetics; D037181:Lectins, C-Type; D051379:Mice; D051761:Paired Box Transcription Factors; D011509:Proteoglycans / Q000235:genetics; D055758:SOX9 Transcription Factor; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D053674:Aggrecans; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D003094:Collagen; D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; D006609:High Mobility Group Proteins; D037181:Lectins, C-Type; D051761:Paired Box Transcription Factors; D011509:Proteoglycans; D055758:SOX9 Transcription Factor; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C508320:Acan protein, mouse; C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; C503815:Scx protein, mouse; C527933:Sox9 protein, mouse; C070835:PAX1 transcription factor