Focal Adhesion Kinase Is Important for Fluid Shear Stress–Induced Mechanotransduction in Osteoblasts
| Autor: | Suzanne R.L. Young, Rita Gerard-O'Riley, Fredrick M. Pavalko, Jae Beom Kim |
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| Rok vydání: | 2009 |
| Předmět: |
Time Factors
Endocrinology Diabetes and Metabolism Integrin Transfection Mechanotransduction Cellular Dinoprostone Focal adhesion Mice Downregulation and upregulation Bone cell medicine Animals Orthopedics and Sports Medicine Osteopontin Phosphorylation RNA Small Interfering Mechanotransduction Prostaglandin E2 Extracellular Signal-Regulated MAP Kinases Protein Kinase Inhibitors Osteoblasts biology Chemistry Osteoblast Original Articles Rats Up-Regulation Cell biology Enzyme Activation medicine.anatomical_structure Biochemistry Cyclooxygenase 2 Enzyme Induction Focal Adhesion Protein-Tyrosine Kinases biology.protein Stress Mechanical Rheology Proto-Oncogene Proteins c-fos medicine.drug |
| Zdroj: | Journal of Bone and Mineral Research. 24:411-424 |
| ISSN: | 0884-0431 |
| DOI: | 10.1359/jbmr.081102 |
| Popis: | Mechanical loading of bone is important for maintenance of bone mass and structural stability of the skeleton. When bone is mechanically loaded, movement of fluid within the spaces surrounding bone cells generates fluid shear stress (FSS) that stimulates osteoblasts, resulting in enhanced anabolic activity. The mechanisms by which osteoblasts convert the external stimulation of FSS into biochemical changes, a process known as mechanotransduction, remain poorly understood. Focal adhesions are prime candidates for transducing external stimuli. Focal adhesion kinase (FAK), a nonreceptor tyrosine kinase found in focal adhesions, may play a key role in mechanotransduction, although its function has not been directly examined in osteoblasts. We examined the role of FAK in osteoblast mechanotransduction using short interfering RNA (siRNA), overexpression of a dominant negative FAK, and FAK(-/-) osteoblasts to disrupt FAK function in calvarial osteoblasts. Osteoblasts were subjected to varying periods oscillatory fluid flow (OFF) from 5 min to 4 h, and several physiologically important readouts of mechanotransduction were analyzed including: extracellular signal-related kinase 1/2 phosphorylation, upregulation of c-fos, cyclooxygenase-2, and osteopontin, and release of prostaglandin E(2). Osteoblasts with disrupted FAK signaling exhibited severely impaired mechanical responses in all endpoints examined. These data indicate the importance of FAK for both short and long periods of FSS-induced mechanotransduction in osteoblasts. |
| Databáze: | OpenAIRE |
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