Activated beta-catenin induces osteoblast differentiation of C3H10T1/2 cells and participates in BMP2 mediated signal transduction.
Wnt glycoproteins are important regulators of cellular differentiation and embryonic development. Some Wnt proteins induce stabilization of beta-catenin which cooperatively regulates gene expression with LEF/Tcf transcription factors. Here we demonstrate a direct role for beta-catenin signaling in osteoblast differentiation and in BMP2-mediated signal transduction. Similar to treatment with BMP-2 protein, ectopic expression of stabilized beta-catenin in C3H10T1/2 cells or activation of endogenous beta-catenin signaling with LiCl induces expression of alkaline phosphatase mRNA and protein, a defined marker of early osteoblast differentiation. Unlike BMP2 protein, stabilized beta-catenin does not induce osteocalcin gene expression, a marker of late osteoblast differentiation. BMP2-induced differentiation also leads to activation of endogenous beta-catenin signaling thus implicating beta-catenin in early steps of BMP2-mediated osteoblast differentiation. Effects of beta-catenin and BMP2 on C3H10T1/2 differentiation are not completely overlapping, implying that some aspects of BMP2-induced differentiation may be mediated by beta-catenin signaling and that beta-catenin can also participate in non-BMP2-dependent differentiation processes.
Bain
Gerard
G
Aventis Cambridge Genomics Center, 26 Landsdowne Street, Cambridge, MA 02139, USA. Gerard.Bain@aventis.com
Müller
Thomas
T
Wang
Xin
X
Papkoff
Jackie
J
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism* / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D048429:Cell Size; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D018021:Lithium Chloride / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology*; D015675:Osteocalcin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta; D051176:beta Catenin
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D051176:beta Catenin; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D018021:Lithium Chloride