The Experts below are selected from a list of 15648 Experts worldwide ranked by ideXlab platform
Toshiyuki Yoneda - One of the best experts on this subject based on the ideXlab platform.
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sox9 family members negatively regulate maturation and calcification of chondrocytes through up regulation of parathyroid hormone related protein
Molecular Biology of the Cell, 2009Co-Authors: Katsuhiko Amano, Kenji Hata, Atsushi Sugita, Yoko Takigawa, K Ono, Makoto Wakabayashi, Mikihiko Kogo, Riko Nishimura, Toshiyuki YonedaAbstract:Sox9 is a transcription factor that plays an essential role in chondrogenesis and has been proposed to inhibit the late stages of endochondral ossification. However, the molecular mechanisms underlying the regulation of chondrocyte maturation and calcification by Sox9 remain unknown. In this study, we attempted to clarify roles of Sox9 in the late stages of chondrocyte differentiation. We found that overexpression of Sox9 alone or Sox9 together with Sox5 and Sox6 (Sox5/6/9) inhibited the maturation and calcification of murine primary chondrocytes and up-regulated parathyroid hormone–related protein (PTHrP) expression in primary chondrocytes and the Mesenchymal Cell Line C3H10T1/2. Sox5/6/9 stimulated the early stages of chondrocyte proliferation and development. In contrast, Sox5/6/9 inhibited maturation and calcification of chondrocytes in organ culture. The inhibitory effects of Sox5/6/9 were rescued by treating with anti-PTHrP antibody. Moreover, Sox5/6/9 bound to the promoter region of the PTHrP gene and up-regulated PTHrP gene promoter activity. Interestingly, we also found that the Sox9 family members functionally collaborated with Ihh/Gli2 signaling to regulate PTHrP expression and chondrocyte differentiation. Our results provide novel evidence that Sox9 family members mediate endochondral ossification by up-regulating PTHrP expression in association with Ihh/Gli2 signaling.
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bmp2 regulates osterix through msx2 and runx2 during osteoblast differentiation
Journal of Biological Chemistry, 2008Co-Authors: Takuma Matsubara, Kenji Hata, Riko Nishimura, Kumiko Kida, Akira Yamaguchi, Fumitaka Ichida, Hiroko Meguro, Hiroyuki Aburatani, Toshiyuki YonedaAbstract:Osterix/Sp7, a member of the Sp1 transcription factor family, plays an essential role in bone formation and osteoblastogenesis. Although Osterix has been shown to be induced by BMP2 in a Mesenchymal Cell Line, the molecular basis of the regulation, expression and function of Osterix during osteoblast differentiation, is not fully understood. Thus we examined the role of BMP2 signaling in the regulation of Osterix using the Mesenchymal Cell Lines C3H10T1/2 and C2C12. Osterix overexpression induced alkaLine phosphatase activity and osteocalcin expression in C2C12 Cells and stimulated calcification of murine primary osteoblasts. Considering that Runx2 overexpression induces Osterix, these results suggest that Osterix functions as downstream of Runx2. Surprisingly, BMP2 treatment induced Osterix expression and alkaLine phosphatase activity in Mesenchymal Cells derived from Runx2-deficient mice. Furthermore, overexpression of Smad1 and Smad4 up-regulated Osterix expression, and an inhibitory Smad, Smad6, markedly suppressed BMP2-induced Osterix expression in the Runx2-deficient Cells. Moreover, overexpression of a homeobox gene, Msx2, which is up-regulated by BMP2 and promotes osteoblastic differentiation, induced Osterix expression in the Runx2-deficient Cells. Knockdown of Msx2 clearly inhibited induction of Osterix by BMP2 in the Runx2-deficient Mesenchymal Cells. Interestingly, microarray analyses using the Runx2-deficient Cells revealed that the role of Osterix was distinct from that of Runx2. These findings suggest that Osterix is regulated via both Runx2-dependent and -independent mechanisms, and that Osterix controls osteoblast differentiation, at least in part, by regulating the expression of genes not controlled by Runx2.
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smad5 and dpc4 are key molecules in mediating bmp 2 induced osteoblastic differentiation of the pluripotent Mesenchymal precursor Cell Line c2c12
Journal of Biological Chemistry, 1998Co-Authors: Riko Nishimura, Toshiyuki Yoneda, S E Harris, Yoichi Kato, Di Chen, Gregory R MundyAbstract:Since the bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGF-beta) superfamily that induce the differentiation of Mesenchymal precursor Cells into the osteogenic Cells, we identified the relevant signaling molecules responsible for mediating BMP-2 effects on Mesenchymal precursor Cells. BMP-2 induces osteoblastic differentiation of the pluripotent Mesenchymal Cell Line C2C12 by increasing alkaLine phosphatase activity and osteocalcin production. As recent studies have demonstrated that cytoplasmic Smad proteins are involved in TGF-beta superfamily signaling, we plan to isolate the relevant Smad family members involved in osteoblastic differentiation. We identified human Smad5, which is highly homologous to Smad1. BMP-2 caused serine phosphorylation of Smad5 as well as Smad1. In contrast, TGF-beta failed to cause serine phosphorylation of Smad1 and Smad5. We found Smad5 is directly activated by BMP type Ia or Ib receptors through physical association with these receptors. Following phosphorylation, Smad5 bound to DPC4, another Smad family member, and the complex was translocated to the nucleus. Overexpression of point-mutated Smad5 (G419S) or a C-terminal deletion mutant DPC4 (DPC4 delta C) blocked the induction of alkaLine phosphatase activity, osteocalcin production, and Smad5-DPC4 signaling cascades upon BMP-2 treatment in C2C12 Cells. These data suggest that activation of Smad5 and subsequent Smad5-DPC4 complex formation are key steps in the BMP signaling pathway, which mediates BMP-2-induced osteoblastic differentiation of the C2C12 Mesenchymal Cells.
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smad5 and dpc4 are key molecules in mediating bmp 2 induced osteoblastic differentiation of the pluripotent Mesenchymal precursor Cell Line c2c12
Journal of Biological Chemistry, 1998Co-Authors: Riko Nishimura, Toshiyuki Yoneda, S E Harris, Yoichi Kato, Di Chen, Gregory R MundyAbstract:Abstract Since the bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β (TGF-β) superfamily that induce the differentiation of Mesenchymal precursor Cells into the osteogenic Cells, we identified the relevant signaling molecules responsible for mediating BMP-2 effects on Mesenchymal precursor Cells. BMP-2 induces osteoblastic differentiation of the pluripotent Mesenchymal Cell Line C2C12 by increasing alkaLine phosphatase activity and osteocalcin production. As recent studies have demonstrated that cytoplasmic Smad proteins are involved in TGF-β superfamily signaling, we plan to isolate the relevant Smad family members involved in osteoblastic differentiation. We identified human Smad5, which is highly homologous to Smad1. BMP-2 caused serine phosphorylation of Smad5 as well as Smad1. In contrast, TGF-β failed to cause serine phosphorylation of Smad1 and Smad5. We found Smad5 is directly activated by BMP type Ia or Ib receptors through physical association with these receptors. Following phosphorylation, Smad5 bound to DPC4, another Smad family member, and the complex was translocated to the nucleus. Overexpression of point-mutated Smad5 (G419S) or a C-terminal deletion mutant DPC4 (DPC4ΔC) blocked the induction of alkaLine phosphatase activity, osteocalcin production, and Smad5-DPC4 signaling cascades upon BMP-2 treatment in C2C12 Cells. These data suggest that activation of Smad5 and subsequent Smad5-DPC4 complex formation are key steps in the BMP signaling pathway, which mediates BMP-2-induced osteoblastic differentiation of the C2C12 Mesenchymal Cells.
S E Harris - One of the best experts on this subject based on the ideXlab platform.
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immortalized mouse floxed bmp2 dental papilla Mesenchymal Cell Lines preserve odontoblastic phenotype and respond to bmp2
Journal of Cellular Physiology, 2010Co-Authors: Li An Wu, Junsheng Feng, Lynn Wang, Yan Dong Mu, Andrew Baker, Kevin J Donly, Jelica Gluhakheinrich, S E HarrisAbstract:Tooth development involves sequential and reciprocal interactions between dental epithelial and Mesenchymal Cells, and proceeds through a series of cytodifferentiations in specific spatial-temporal patterns (Linde and Goldberg, 1993). Dentinogenesis is a complex process in which multiple signaling pathways converge to induce dentin formation and is controlled by many growth and transcription factors (Thesleff, 2003). The bone morphogenetic proteins (Bmps) are structurally related to the transforming growth factor beta (TGF-β) superfamily and were originally identified by their capacity to induce ectopic bone formation in rodents (Urist, 1965; Wozney et al., 1988). Members of the Bmp family have diverse biological functions during embryonic development (Hogan, 1996; Wu et al., 2003) including a vital role in osteogenesis (Chen et al., 2004; Rosen, 2009). Among the Bmp family members, Bmp2 has been extensively studied for its various biological functions during chondrogenic and osteogenic differentiation (Reddi, 1997; Ducy and Karsenty, 2000). Also, Bmp2 has been shown to promote dental pulp stem Cell commitment to the odontoblast Lineage in vitro (Yang et al., 2009) and induces dental pulp Cell differentiation and mineralization in vitro and in vivo (Nakashima, 2005; Chen et al., 2008). However, detail understandings of the molecular mechanisms of Bmp2 exerting its effects on tooth development and formation remain elusive in particular during postnatal tooth development as homozygous mutant embryos for Bmp2 show developmental abnormalities and die at embryo day 9.5 (Zhang and Bradley, 1996). Recently, conditional Bmp2 knock out (cBmp2-KO) mice were generated and revealed important roles of Bmp2 in later stages of osteogenesis (Bandyopadhyay et al., 2006) and bone fracture healing (Tsuji et al., 2006) as well as other organ development (Ma et al., 2005; Rivera-Feliciano and Tabin, 2006; Lee et al., 2007; Singh et al., 2008). However, roles of Bmp2 during tooth development and formation have not been completely understood. Unlike bone and other tissues, it is relatively hard to collect enough amounts of dental tissues from a single tooth. Therefore, generation of a floxed Bmp2 dental papilla Mesenchymal Cell Line would be a valuable tool for studying the effects of Bmp2 on dental Cell Lineages as well as relevant molecular events involved in matrix mineralization and dentin regeneration. Such information will help realize the potential of BMP2 as therapeutic agent and for the rational targeting of specific Bmp2 to the appropriate clinical indication. In this study, we established an immortalized mouse floxed Bmp2 dental papilla Mesenchymal Cell Line using transduction of simian phenotypic and virus 40 T-antigen (SV40). We further observed these Cell growth rates and their genotypic and phenotypic characteristics as compared to primary Cells. Finally, we tested whether these immortalized Cells were inducible by growth factors.
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smad5 and dpc4 are key molecules in mediating bmp 2 induced osteoblastic differentiation of the pluripotent Mesenchymal precursor Cell Line c2c12
Journal of Biological Chemistry, 1998Co-Authors: Riko Nishimura, Toshiyuki Yoneda, S E Harris, Yoichi Kato, Di Chen, Gregory R MundyAbstract:Since the bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGF-beta) superfamily that induce the differentiation of Mesenchymal precursor Cells into the osteogenic Cells, we identified the relevant signaling molecules responsible for mediating BMP-2 effects on Mesenchymal precursor Cells. BMP-2 induces osteoblastic differentiation of the pluripotent Mesenchymal Cell Line C2C12 by increasing alkaLine phosphatase activity and osteocalcin production. As recent studies have demonstrated that cytoplasmic Smad proteins are involved in TGF-beta superfamily signaling, we plan to isolate the relevant Smad family members involved in osteoblastic differentiation. We identified human Smad5, which is highly homologous to Smad1. BMP-2 caused serine phosphorylation of Smad5 as well as Smad1. In contrast, TGF-beta failed to cause serine phosphorylation of Smad1 and Smad5. We found Smad5 is directly activated by BMP type Ia or Ib receptors through physical association with these receptors. Following phosphorylation, Smad5 bound to DPC4, another Smad family member, and the complex was translocated to the nucleus. Overexpression of point-mutated Smad5 (G419S) or a C-terminal deletion mutant DPC4 (DPC4 delta C) blocked the induction of alkaLine phosphatase activity, osteocalcin production, and Smad5-DPC4 signaling cascades upon BMP-2 treatment in C2C12 Cells. These data suggest that activation of Smad5 and subsequent Smad5-DPC4 complex formation are key steps in the BMP signaling pathway, which mediates BMP-2-induced osteoblastic differentiation of the C2C12 Mesenchymal Cells.
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smad5 and dpc4 are key molecules in mediating bmp 2 induced osteoblastic differentiation of the pluripotent Mesenchymal precursor Cell Line c2c12
Journal of Biological Chemistry, 1998Co-Authors: Riko Nishimura, Toshiyuki Yoneda, S E Harris, Yoichi Kato, Di Chen, Gregory R MundyAbstract:Abstract Since the bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β (TGF-β) superfamily that induce the differentiation of Mesenchymal precursor Cells into the osteogenic Cells, we identified the relevant signaling molecules responsible for mediating BMP-2 effects on Mesenchymal precursor Cells. BMP-2 induces osteoblastic differentiation of the pluripotent Mesenchymal Cell Line C2C12 by increasing alkaLine phosphatase activity and osteocalcin production. As recent studies have demonstrated that cytoplasmic Smad proteins are involved in TGF-β superfamily signaling, we plan to isolate the relevant Smad family members involved in osteoblastic differentiation. We identified human Smad5, which is highly homologous to Smad1. BMP-2 caused serine phosphorylation of Smad5 as well as Smad1. In contrast, TGF-β failed to cause serine phosphorylation of Smad1 and Smad5. We found Smad5 is directly activated by BMP type Ia or Ib receptors through physical association with these receptors. Following phosphorylation, Smad5 bound to DPC4, another Smad family member, and the complex was translocated to the nucleus. Overexpression of point-mutated Smad5 (G419S) or a C-terminal deletion mutant DPC4 (DPC4ΔC) blocked the induction of alkaLine phosphatase activity, osteocalcin production, and Smad5-DPC4 signaling cascades upon BMP-2 treatment in C2C12 Cells. These data suggest that activation of Smad5 and subsequent Smad5-DPC4 complex formation are key steps in the BMP signaling pathway, which mediates BMP-2-induced osteoblastic differentiation of the C2C12 Mesenchymal Cells.
Riko Nishimura - One of the best experts on this subject based on the ideXlab platform.
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sox9 family members negatively regulate maturation and calcification of chondrocytes through up regulation of parathyroid hormone related protein
Molecular Biology of the Cell, 2009Co-Authors: Katsuhiko Amano, Kenji Hata, Atsushi Sugita, Yoko Takigawa, K Ono, Makoto Wakabayashi, Mikihiko Kogo, Riko Nishimura, Toshiyuki YonedaAbstract:Sox9 is a transcription factor that plays an essential role in chondrogenesis and has been proposed to inhibit the late stages of endochondral ossification. However, the molecular mechanisms underlying the regulation of chondrocyte maturation and calcification by Sox9 remain unknown. In this study, we attempted to clarify roles of Sox9 in the late stages of chondrocyte differentiation. We found that overexpression of Sox9 alone or Sox9 together with Sox5 and Sox6 (Sox5/6/9) inhibited the maturation and calcification of murine primary chondrocytes and up-regulated parathyroid hormone–related protein (PTHrP) expression in primary chondrocytes and the Mesenchymal Cell Line C3H10T1/2. Sox5/6/9 stimulated the early stages of chondrocyte proliferation and development. In contrast, Sox5/6/9 inhibited maturation and calcification of chondrocytes in organ culture. The inhibitory effects of Sox5/6/9 were rescued by treating with anti-PTHrP antibody. Moreover, Sox5/6/9 bound to the promoter region of the PTHrP gene and up-regulated PTHrP gene promoter activity. Interestingly, we also found that the Sox9 family members functionally collaborated with Ihh/Gli2 signaling to regulate PTHrP expression and chondrocyte differentiation. Our results provide novel evidence that Sox9 family members mediate endochondral ossification by up-regulating PTHrP expression in association with Ihh/Gli2 signaling.
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bmp2 regulates osterix through msx2 and runx2 during osteoblast differentiation
Journal of Biological Chemistry, 2008Co-Authors: Takuma Matsubara, Kenji Hata, Riko Nishimura, Kumiko Kida, Akira Yamaguchi, Fumitaka Ichida, Hiroko Meguro, Hiroyuki Aburatani, Toshiyuki YonedaAbstract:Osterix/Sp7, a member of the Sp1 transcription factor family, plays an essential role in bone formation and osteoblastogenesis. Although Osterix has been shown to be induced by BMP2 in a Mesenchymal Cell Line, the molecular basis of the regulation, expression and function of Osterix during osteoblast differentiation, is not fully understood. Thus we examined the role of BMP2 signaling in the regulation of Osterix using the Mesenchymal Cell Lines C3H10T1/2 and C2C12. Osterix overexpression induced alkaLine phosphatase activity and osteocalcin expression in C2C12 Cells and stimulated calcification of murine primary osteoblasts. Considering that Runx2 overexpression induces Osterix, these results suggest that Osterix functions as downstream of Runx2. Surprisingly, BMP2 treatment induced Osterix expression and alkaLine phosphatase activity in Mesenchymal Cells derived from Runx2-deficient mice. Furthermore, overexpression of Smad1 and Smad4 up-regulated Osterix expression, and an inhibitory Smad, Smad6, markedly suppressed BMP2-induced Osterix expression in the Runx2-deficient Cells. Moreover, overexpression of a homeobox gene, Msx2, which is up-regulated by BMP2 and promotes osteoblastic differentiation, induced Osterix expression in the Runx2-deficient Cells. Knockdown of Msx2 clearly inhibited induction of Osterix by BMP2 in the Runx2-deficient Mesenchymal Cells. Interestingly, microarray analyses using the Runx2-deficient Cells revealed that the role of Osterix was distinct from that of Runx2. These findings suggest that Osterix is regulated via both Runx2-dependent and -independent mechanisms, and that Osterix controls osteoblast differentiation, at least in part, by regulating the expression of genes not controlled by Runx2.
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smad5 and dpc4 are key molecules in mediating bmp 2 induced osteoblastic differentiation of the pluripotent Mesenchymal precursor Cell Line c2c12
Journal of Biological Chemistry, 1998Co-Authors: Riko Nishimura, Toshiyuki Yoneda, S E Harris, Yoichi Kato, Di Chen, Gregory R MundyAbstract:Since the bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGF-beta) superfamily that induce the differentiation of Mesenchymal precursor Cells into the osteogenic Cells, we identified the relevant signaling molecules responsible for mediating BMP-2 effects on Mesenchymal precursor Cells. BMP-2 induces osteoblastic differentiation of the pluripotent Mesenchymal Cell Line C2C12 by increasing alkaLine phosphatase activity and osteocalcin production. As recent studies have demonstrated that cytoplasmic Smad proteins are involved in TGF-beta superfamily signaling, we plan to isolate the relevant Smad family members involved in osteoblastic differentiation. We identified human Smad5, which is highly homologous to Smad1. BMP-2 caused serine phosphorylation of Smad5 as well as Smad1. In contrast, TGF-beta failed to cause serine phosphorylation of Smad1 and Smad5. We found Smad5 is directly activated by BMP type Ia or Ib receptors through physical association with these receptors. Following phosphorylation, Smad5 bound to DPC4, another Smad family member, and the complex was translocated to the nucleus. Overexpression of point-mutated Smad5 (G419S) or a C-terminal deletion mutant DPC4 (DPC4 delta C) blocked the induction of alkaLine phosphatase activity, osteocalcin production, and Smad5-DPC4 signaling cascades upon BMP-2 treatment in C2C12 Cells. These data suggest that activation of Smad5 and subsequent Smad5-DPC4 complex formation are key steps in the BMP signaling pathway, which mediates BMP-2-induced osteoblastic differentiation of the C2C12 Mesenchymal Cells.
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smad5 and dpc4 are key molecules in mediating bmp 2 induced osteoblastic differentiation of the pluripotent Mesenchymal precursor Cell Line c2c12
Journal of Biological Chemistry, 1998Co-Authors: Riko Nishimura, Toshiyuki Yoneda, S E Harris, Yoichi Kato, Di Chen, Gregory R MundyAbstract:Abstract Since the bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β (TGF-β) superfamily that induce the differentiation of Mesenchymal precursor Cells into the osteogenic Cells, we identified the relevant signaling molecules responsible for mediating BMP-2 effects on Mesenchymal precursor Cells. BMP-2 induces osteoblastic differentiation of the pluripotent Mesenchymal Cell Line C2C12 by increasing alkaLine phosphatase activity and osteocalcin production. As recent studies have demonstrated that cytoplasmic Smad proteins are involved in TGF-β superfamily signaling, we plan to isolate the relevant Smad family members involved in osteoblastic differentiation. We identified human Smad5, which is highly homologous to Smad1. BMP-2 caused serine phosphorylation of Smad5 as well as Smad1. In contrast, TGF-β failed to cause serine phosphorylation of Smad1 and Smad5. We found Smad5 is directly activated by BMP type Ia or Ib receptors through physical association with these receptors. Following phosphorylation, Smad5 bound to DPC4, another Smad family member, and the complex was translocated to the nucleus. Overexpression of point-mutated Smad5 (G419S) or a C-terminal deletion mutant DPC4 (DPC4ΔC) blocked the induction of alkaLine phosphatase activity, osteocalcin production, and Smad5-DPC4 signaling cascades upon BMP-2 treatment in C2C12 Cells. These data suggest that activation of Smad5 and subsequent Smad5-DPC4 complex formation are key steps in the BMP signaling pathway, which mediates BMP-2-induced osteoblastic differentiation of the C2C12 Mesenchymal Cells.
John C Lee - One of the best experts on this subject based on the ideXlab platform.
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cartilage derived morphogenetic proteins induce osteogenic gene expression in the c2c12 Mesenchymal Cell Line
Journal of Cellular Biochemistry, 2005Co-Authors: Leechuan C Yeh, Alicia D Tsai, John C LeeAbstract:Cartilage-derived morphogenetic protein-1, -2, and -3 (CDMP-1, -2, and -3) are members of the bone morphogenetic protein (BMP) family and have been shown to exhibit a variety of biological activities. In the present study, effects of these CDMPs on the temporal and spatial expression of genes in the pluripotent Mesenchymal Cell Line C2C12 were examined. Cells cultured in the presence of CDMPs lost the characteristic elongated shape of myoblasts. At the molecular level, CDMP treatment did not change the mRNA expression of MyoD, aggrecan, Six1, and tendin. Scleraxis mRNA level was reduced by CDMP treatment. CDMP-1 and -3, but not CDMP-2, stimulated expression of osteogenic markers, such as alkaLine phosphatase (AP), osteocalcin (OC), BSP, and type I collagen, in a dose- and time-dependent manner. With few exceptions, the three CDMPs changed, with different potencies, the expression profile of different members of the BMP family in a similar temporal pattern. Except at the late phase of treatment, CDMP treatment did not change the expression of ActR-IA, BMPR-IA, BMPR-IB, BMPR-II, and ALK-7 mRNAs. Based on the current data, the CDMPs appear to be able to stimulate the C2C12 Cells to differentiate into the osteoblast pathway.
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osteogenic protein 1 op 1 bmp 7 induces osteoblastic Cell differentiation of the pluripotent Mesenchymal Cell Line c2c12
Journal of Cellular Biochemistry, 2002Co-Authors: Leechuan C Yeh, Alicia D Tsai, John C LeeAbstract:The effects of Osteogenic Protein-1 (OP-1, BMP-7) on the differentiation of the pluripotent Mesenchymal Cell Line, C2C12, were examined. OP-1 at 50 ng/ml partially inhibited myotube formation in C2C12 Cells, while OP-1 at 200 ng/ml completely inhibited myotube formation and induced the formation of Cells displaying osteoblastic morphology. High concentrations of OP-1 elevated the alkaLine phosphatase (AP) activity dramatically, both as a function of time and OP-1 concentration. Osteocalcin (OC) mRNA expression was detected as early as 8 days in OP-1-treated cultures and subsequently increased considerably. Expression of bone sialoprotein (BSP) mRNA was low in control cultures and stimulated by OP-1. Collagen type I mRNA expression was enhanced by OP-1 during the early days in culture, but gradually decreased thereafter. MyoD mRNA expression, high in control cultures, was suppressed by OP-1 in a dose- and time-dependent manner. OP-1 enhanced ActR-I mRNA expression and significantly elevated the mRNA expressions of BMP-1, BMP-4, BMP-5, GDF-6, and GDF-8. The present results indicate that OP-1 is a potent inducer of C2C12 differentiation into osteoblastic Cells.
Wade Bushman - One of the best experts on this subject based on the ideXlab platform.
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prostate stromal and urogenital sinus Mesenchymal Cell Lines for investigations of stromal epithelial interactions
Differentiation, 2008Co-Authors: Aubie Shaw, Steven Attia, Wade BushmanAbstract:Bidirectional signaling between the urogenital sinus epithelium and mesenchyme is an essential element of prostate development that regulates ductal morphogenesis, growth, and differentiation. Comparable interactions between the epithelium and stroma in the adult prostate appear to regulate normal growth homeostasis. Alterations in the stromal–epithelial dialogue that recapitulate features of the Mesenchymal–epithelial interactions of development may play a critical role in the development of benign prostatic hyperplasia and in the progression of prostate cancer. For this reason, the Mesenchymal–epithelial interactions of development are of considerable interest. In this review, we provide an overview of the Mesenchymal contribution to rodent prostate development with an emphasis on the stage just before ductal budding (embryonic day 16; E16) and describe the isolation, characterization and utility of a newly established E16 urogenital sinus Mesenchymal Cell Line.
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Isolation and characterization of an immortalized mouse urogenital sinus mesenchyme Cell Line.
The Prostate, 2006Co-Authors: Aubie K. Shaw, John N Papadopoulos, Curtis A. Johnson, Wade BushmanAbstract:BACKGROUND Stromal-epithelial signaling plays an important role in prostate development and cancer progression. Study of these interactions will be facilitated by the use of suitable prostate Cell Lines in appropriate model systems. METHODS We have isolated an immortalized prostate Mesenchymal Cell Line from the mouse E16 urogenital sinus (UGS). We characterized its expression of stromal differentiation markers, response to androgen stimulation, ability to induce and participate in prostate morphogenesis, response to Shh stimulation, and interaction with prostate epithelial Cells. RESULTS UGSM-2 Cells express vimentin and smooth muscle actin, but not the mature smooth muscle markers myosin and desmin. This expression profile is consistent with a myofibroblast phenotype. Unlike other fibroblasts such as 3T3, UGSM-2 Cells express androgen receptor mRNA and androgen stimulation increases proliferation. UGSM-2 Cells are viable when grafted with embryonic UGS under the renal capsule and participate in glandular morphogenesis, but are not capable of inducing prostate morphogenesis of isolated UGS epithelium. Co-culture of UGSM-2 Cells with human BPH-1 Cells or co-grafting in vivo results in organized clusters of BPH-1 Cells surrounded by a mantle of UGSM-2 Cells. UGSM-2 Cells are responsive to Sonic hedgehog (Shh), an important signaling factor in prostate development, and mimic the transcriptional response of the intact UGS mesenchyme. In co-cultures with BPH-1, UGSM-2 Cells exhibit a robust transcriptional response to Shh secreted by BPH-1. CONCLUSIONS UGSM-2 is a urogenital sinus mesenchyme Cell Line that can be used to study stromal-epithelial interactions that are important in prostate biology. Prostate 66: 1347–1358, 2006. © 2006 Wiley-Liss, Inc.