BMP-2-modulated chondrogenic differentiation in vitro involves down-regulation of membrane-bound beta-catenin.
Bone morphogenetic proteins (BMPs) are important regulators of cellular differentiation and embryonic development. Beta catenin mediated nuclear signaling has been implicated in BMP-2-modulated chondrogenic differentiation in the pluripotential stem cell line C3H10T1/2. However, there is little information on the functional role of beta catenin in BMP-2-modulated differentiation of primary nontransformed mesenchymal cells. Here, we present evidence to show that BMP-2-induced chondrogenic differentiation in high-density primary mesenchymal culture is associated with a significant decrease in membrane-bound beta catenin by 72 hours compared to controls. Nuclear localization of beta catenin is not detectable by immunofluorescence and the TCF-responsive reporter vector TOPFLASH shows only background activity during chondrogenic differentiation. BMP-2-treated cultures show reduced cell-cell adhesion by 72 hours, which correlates with the changes in levels of membrane-bound beta catenin. Up-regulation of membrane-bound beta catenin blocks the effect of BMP-2 on both chondrogenic differentiation and cell-cell adhesiveness. These findings suggest that BMP-2 can modulate the adhesivity of adherens junctions through regulation of membrane bound beta catenin.
Zhang
Wei V
WV
Department of Surgery, Faculty of Medicine and Health Science, The University of Auckland, Auckland, New Zealand.
Stott
N Susan
NS
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D015820:Cadherins / Q000235:genetics; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology*; D002642:Chick Embryo; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D018878:Limb Buds; D018021:Lithium Chloride / Q000494:pharmacology; D008648:Mesoderm / Q000166:cytology; D015534:Trans-Activators / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D051176:beta Catenin
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D051176:beta Catenin; D018021:Lithium Chloride