Mechanical stimulation prevents osteocyte apoptosis: requirement of integrins, Src kinases, and ERKs
Autor: | J. I. Aguirre, Lilian I. Plotkin, I. Mathov, Teresita Bellido, A. M. Parfitt, Stavros C. Manolagas |
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Rok vydání: | 2005 |
Předmět: |
Integrins
Cell signaling MAP Kinase Signaling System Physiology Integrin Apoptosis Beta-Cyclodextrins Caveolae Osteocytes Cell Line Mice Tubulin Physical Stimulation medicine Animals RNA Messenger Mechanotransduction Extracellular Signal-Regulated MAP Kinases Cytoskeleton Glucocorticoids Etoposide Nucleic Acid Synthesis Inhibitors biology Chemistry Kinase beta-Cyclodextrins Cell Biology Actins Cell biology src-Family Kinases medicine.anatomical_structure Osteocyte Carcinogens biology.protein Proto-oncogene tyrosine-protein kinase Src |
Zdroj: | American Journal of Physiology-Cell Physiology. 289:C633-C643 |
ISSN: | 1522-1563 0363-6143 |
DOI: | 10.1152/ajpcell.00278.2004 |
Popis: | Osteocytes, former osteoblasts entombed in the bone matrix, form an extensive cell communication network that is thought to detect microdamage and mechanical strains and to transmit signals leading to repair and compensatory bone augmentation or reduction. Bone active hormones and drugs control the integrity of this network by regulating osteocyte apoptosis, which might be a determinant of bone strength. Herein we demonstrate that mechanical stimulation by stretching activates the ERKs, which in turn are responsible for the attenuation of osteocyte apoptosis. The effect of osteocyte stretching is transmitted by integrins and cytoskeletal and catalytic molecules, such as Src kinases. Stretch-induced antiapoptosis also requires nuclear translocation of ERKs and new gene transcription. The evidence linking mechanical stimulation, activation of an integrin/cytoskeleton/Src/ERK signaling pathway, and osteocyte survival provides a mechanistic basis for the profound role of mechanical forces, or lack thereof, on skeletal health and disease. |
Databáze: | OpenAIRE |
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