Requirement of autocrine signaling by bone morphogenetic protein-4 for chondrogenic differentiation of ATDC5 cells.
Mouse EC cell line ATDC5 undergoes differentiation to form cartilage nodules via the cellular condensation stage in the presence of insulin. ATDC5 cells expressed transcripts for bone morphogenetic protein-4 (BMP-4), and type IA and type II BMP receptors. Moreover, cells retained responsiveness to BMP-4, which induced the formation of chondrocytes in the culture. When transfected with a kinase domain-truncated type IA BMP receptor construct, cells failed to undergo differentiation beyond the condensation stage even in the presence of insulin. The soluble form of type IA BMP receptor also blocked the formation of chondrocytes in a dose dependent manner. These lines of evidence suggested that autocrine BMP-4 signaling is required for the conversion of chondrogenic precursor cells into chondrocytes.
Shukunami
C
C
Department of Molecular Interaction and Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, Japan.
Akiyama
H
H
Nakamura
T
T
Hiraki
Y
Y
D000818:Animals; D055415:Bone Morphogenetic Protein 4; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002356:Cartilage / Q000254:growth & development*; D002454:Cell Differentiation; D002460:Cell Line; D019902:Chondrocytes / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
C525809:BMP4 protein, human; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D007328:Insulin; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D017346:Protein Serine-Threonine Kinases; C498211:BMPR1A protein, human; C498218:BMPR2 protein, human; C498219:Bmpr2 protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II