Activation of epidermal growth factor receptor gene is involved in transforming growth factor-beta-mediated fibronectin expression in a chondrocyte progenitor cell line.
Chondrocytes produce many types of ECM to maintain elasticity and plasticity in articular cartilage of revolute joints. Both transforming growth factor beta (TGF-beta) and bone morphogenetic proteins (BMPs) induce extracellular matrix proteins such as type IIalpha1 collagen and aggrecan during chondrogenic differentiation in vitro. However, differences in the matrix gene expression pattern by the stimulation of TGF-betas and BMPs remains unclear. In the present study, we created a customized PCR-based ECM array to investigate the pattern of ECM expression genes in the chondrocyte progenitor cell line ATDC5, that was stimulated by TGF-betas or BMPs. Fibronectin (Fn) expression was drastically induced after TGF-beta stimulation, but not BMP-4. Epidermal growth factor receptor (Egfr) gene was also significantly activated in TGF-beta1-induced chondrogenic differentiation as compared to BMP-4-mediated differentiation. Furthermore, EGFR-knockdown assay of the cells showed decreasing Fn expression during TGF-beta1-induced chondrogenic differentiation. These data indicated that Egfr gene activation by TGF-beta is involved in the differences in the expression of cellular matrix genes such as Fn, as compared to the expression pattern induced by BMPs.
Takeda
Haruhiko
H
Department of Bone and Joint Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
Inoue
Hirofumi
H
Kutsuna
Tastuhiko
T
Matsushita
Natsuki
N
Takahashi
Toshiaki
T
Watanabe
Shohei
S
Higashiyama
Shigeki
S
Yamamoto
Haruyasu
H
D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D034741:RNA, Small Interfering / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D055415:Bone Morphogenetic Protein 4; D005353:Fibronectins; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D066246:ErbB Receptors