Mechanical stimulation prevents osteocyte apoptosis: requirement of integrins, Src kinases, and ERKs

Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, and Central Arkansas Veterans Healthcare System, University of Arkansas for Medical Sciences, Little Rock, Arkansas Submitted 11 June 2004 ; accepted in final form 30 April 2005 Osteocytes, former osteobla...

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Published in:American Journal of Physiology: Cell Physiology 2005-09, Vol.289 (3), p.C633-C643
Main Authors: Plotkin, L. I, Mathov, I, Aguirre, J. I, Parfitt, A. M, Manolagas, S. C, Bellido, T
Format: Article
Language:English
Subjects:
Actins - metabolism
Animals
Apoptosis - drug effects
Apoptosis - physiology
beta-Cyclodextrins - pharmacology
Carcinogens - pharmacology
Caveolae - drug effects
Caveolae - physiology
Cell Line
Cytoskeleton - metabolism
Etoposide - pharmacology
Extracellular Signal-Regulated MAP Kinases - metabolism
Glucocorticoids - pharmacology
Integrins - metabolism
MAP Kinase Signaling System - drug effects
MAP Kinase Signaling System - physiology
Mice
Nucleic Acid Synthesis Inhibitors - pharmacology
Osteocytes - cytology
Osteocytes - enzymology
Physical Stimulation
RNA, Messenger - metabolism
src-Family Kinases - metabolism
Tubulin - metabolism
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Summary:Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, and Central Arkansas Veterans Healthcare System, University of Arkansas for Medical Sciences, Little Rock, Arkansas Submitted 11 June 2004 ; accepted in final form 30 April 2005 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. bone; mechanotransduction; osteoblastic cells; caveolae; stretching Address for reprint requests and other correspondence: T. Bellido, Div. of Endocrinology and Metabolism, Univ. of Arkansas for Medical Sciences, 4301 West Markham, Mail Slot 587, Little Rock, AR 72205 (e-mail: tmbellido{at}uams.edu )
ISSN:0363-6143
1522-1563
DOI:10.1152/ajpcell.00278.2004