Fluid Shear Stress Induces ?-Catenin Signaling in Osteoblasts
| Autor: | Fredrick M. Pavalko, Joseph P. Bidwell, Suzanne M. Norvell, Marta Alvarez |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Cell signaling
Time Factors Endocrinology Diabetes and Metabolism Immunoblotting Electrophoretic Mobility Shift Assay Protein Serine-Threonine Kinases Biology Mice Endocrinology Genes Reporter GSK-3 Cell Line Tumor Proto-Oncogene Proteins Gene expression medicine Animals Orthopedics and Sports Medicine Phosphorylation Fluorescent Antibody Technique Indirect Protein kinase B Cells Cultured beta Catenin Cell Nucleus Osteoblasts Cadherin Skull Glycogen Synthase Kinases Osteoblast 3T3 Cells Precipitin Tests Molecular biology Rats Cell biology Cytoskeletal Proteins medicine.anatomical_structure Animals Newborn Mutation Trans-Activators Stress Mechanical Proto-Oncogene Proteins c-akt Nucleus Signal Transduction |
| Zdroj: | Calcified Tissue International. 75:396-404 |
| ISSN: | 1432-0827 0171-967X |
| DOI: | 10.1007/s00223-004-0213-y |
| Popis: | beta-Catenin plays a dual role in cells: one at cell-cell junctions and one regulating gene transcription together with TCF (T-cell Factor) in the nucleus. Recently, a role for beta-catenin in osteoblast differentiation and gene expression has begun to be elucidated. Herein we investigated the effects of fluid shear stress (FSS) on beta-catenin signaling. FSS is a well-characterized anabolic stimulus for osteoblasts; however, the molecular mechanisms for the effects of this stimulation remain largely unknown. We found that 1 hour of laminar FSS (10 dynes/cm(2)) induced translocation of beta-catenin to the nucleus and activated a TCF-reporter gene. Analysis of upstream signals that may regulate beta-catenin signaling activity revealed two potential mechanisms for increased beta-catenin signaling. First, FSS induced a transient, but significant, increase in the phosphorylation of both glycogen synthase kinase 3beta (GSK-3beta) and Akt. Second, FSS reduced the levels of beta-catenin associated with N-cadherin, suggesting that less sequestration of beta-catenin by cadherins occurs in osteoblasts subjected to FSS. Functional analysts of potential genes regulated by beta-catenin signaling in osteoblasts revealed two novel observations. First, endogenous, nuclear beta-catenin purified from osteoblasts formed a complex with a TCF -binding element in the cyclooxygenase-2 promoter, and, second, overexpression of either a constitutively active beta-catenin molecule or inhibition of GSK-3beta activity increased basal cyclooxygenase-2 levels. Together, these data demonstrate for the first time that FSS modulates the activity of both GSK-3beta and beta-catenin and that these signaling molecules regulate cyclooxygenase-2 expression in osteoblasts. |
| Databáze: | OpenAIRE |
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