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Collagen Gene Promoter (collagen + gene_promoter)
Selected AbstractsGenkwanin up-regulates the transcriptional activation of human type vii collagen gene promoterINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 4 2007N. Takebayashi In a recent study, stimulating the formation of anchoring fibrils at the basement membrane zone in skin contributed to preventing skin ageing, such as wrinkle formation. Expression of the type VII collagen gene induces the formation of anchoring fibrils composed mainly of collagen type VII. We therefore transiently transfected a keratinocyte cell line with the plasmids containing type VII collagen gene promoter located upstream of the luciferase gene. We investigated the promoter activity under the presence of flavonoids and we found that Genkwanin up-regulates the transcriptional activation of human type VII collagen gene promoter. [source] Inactivation of Pten in Osteo-Chondroprogenitor Cells Leads to Epiphyseal Growth Plate Abnormalities and Skeletal Overgrowth,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2007Alice Fiona Ford-Hutchinson Abstract To study the role of the Pten tumor suppressor in skeletogenesis, we generated mice lacking this key phosphatidylinositol 3,-kinase pathway regulator in their osteo-chondroprogenitors. A phenotype of growth plate dysfunction and skeletal overgrowth was observed. Introduction: Skeletogenesis is a complex process relying on a variety of ligands that activate a range of intracellular signal transduction pathways. Although many of these stimuli are known to activate phosphatidylinositol 3,-kinase (PI3K), the function of this pathway during cartilage development remains nebulous. To study the role of PI3K during skeletogenesis, we used mice deficient in a negative regulator of PI3K signaling, the tumor suppressor, Pten. Materials and Methods:Pten gene deletion in osteo-chondrodroprogenitors was obtained by interbreeding mice with loxP-flanked Pten exons with mice expressing the Cre recombinase under the control of the type II collagen gene promoter (Ptenflox/flox:Col2a1Cre mice). Phenotypic analyses included microcomputed tomography and immunohistochemistry techniques. Results: ,CT revealed that Ptenflox/flox:Col2a1Cre mice exhibited both increased skeletal size, particularly of vertebrae, and massive trabeculation accompanied by increased cortical thickness. Primary spongiosa development and perichondrial bone collar formation were prominent in Ptenflox/flox:Col2a1Cre mice, and long bone growth plates were disorganized and showed both matrix overproduction and evidence of accelerated hypertrophic differentiation (indicated by an altered pattern of type X collagen and alkaline phosphatase expression). Consistent with increased PI3K signaling, Pten-deficient chondrocytes showed increased phospho-PKB/Akt and phospho-S6 immunostaining, reflective of increased mTOR and PDK1 activity. Interestingly, no significant change in growth plate proliferation was seen in Pten-deficient mice, and growth plate fusion was found at 6 months. Conclusions: By virtue of its ability to modulate a key signal transduction pathway responsible for integrating multiple stimuli, Pten represents an important regulator of both skeletal size and bone architecture. [source] Down-Regulation of Procollagen ,1[I] Messenger RNA by Titanium Particles Correlates with Nuclear Factor ,B (NF-,B) Activation and Increased Rel A and NF-,B1 Binding to the Collagen PromoterJOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2001Kenneth A. Roebuck Abstract Previously, we showed that exposure of human osteoblasts to titanium particles stimulates protein tyrosine phosphorylation (PTP), activates the transcription factor nuclear factor ,B (NF-,B), and causes an approximately 50% decrease in the steady-state messenger RNA (mRNA) level of procollagen ,1[I]. In this study, we identify three NF-,B binding sites within the human procollagen ,1[I] gene promoter, show that titanium particles stimulate their binding of the NF-,B subunits Rel A (p65) and NF-,B1 (p50), and find NF-,B activation correlates with collagen gene suppression by titanium particles in osteoblasts. Protein tyrosine kinase (PTK) inhibitors, which significantly reduce the suppressive effect of titanium particles on collagen gene expression, inhibited NF-,B binding activity showing that titanium particle stimulation of PTK signals in osteoblasts are critical for both NF-,B activation and collagen gene expression. The antioxidant pyrrolidine dithiocarbamate (PDTC), which also inhibits the titanium particle suppression of collagen, abrogated the titanium particle activation of NF-,B, suggesting the involvement of redox signals in NF-,B-mediated collagen gene expression. The RNA polymerase II inhibitor actinomycin D (Act D) decreased procollagen ,1[I] mRNA expression and effectively blocked the titanium-induced suppressive effect, suggesting that titanium particles activate a cascade of signals in osteoblasts, which result in a suppression of procollagen ,1[I] mRNA. Collectively, these results show that titanium particles can activate NF-,B signaling in osteoblasts and suggest that NF-,B binding to the collagen gene promoter has a functional role in the down-regulation of procollagen ,1[I] gene transcription. [source] | ||||||||||