title: The role of integrin α(V)β(3) in osteocyte mechanotransduction.
abstract: Recent in vivo studies have proposed that integrin αvβ3 attachments between osteocyte cell processes and the extracellular matrix may facilitate mechanosensation in bone. However the role of these attachments in osteocyte biochemical response to mechanical stimulus has yet to be investigated. With this in mind, the objective of this study was to determine the effect of blocking integrin αvβ3 function on the biochemical response of osteocytes to mechanical stimulus. Antagonists specific to integrin subunit β3 were used to block integrin αvβ3 on MLO-Y4 mouse osteocytes. After treatment, cells were subjected to laminar oscillatory fluid flow stimulus (1 Pa, 1 Hz) for one hour. Fluorescent staining was performed to visualise cell morphology. Prostaglandin E2 (PGE2) release was assayed using an enzyme immunoassay and qRT-PCR was used to analyse the relative expression of cyclooxygenase-2 (COX-2), receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG). Our results show that blocking integrin αvβ3 disrupts osteocyte morphology, causing a reduction in spread area and process retraction. Integrin αvβ3 blocking also disrupted COX-2 expression and PGE2 release in response to fluid shear stress. Taken together, the results of this study indicate that integrin αvβ3 is essential for the maintenance of osteocyte cell processes and also for mechanosensation and mechanotransduction by osteocytes. A better understanding of this process may lead to the development of novel treatments for bone pathologies where mechanosensitivity is thought to be compromised.
authors.affiliation: Centre for Biomechanics Research (BMEC), Mechanical and Biomedical Engineering, National University of Ireland, Galway, Ireland; National Centre for Biomedical Engineering Sciences (NCBES), National University of Ireland, Galway, Ireland.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Haugh
authors.affiliation: Centre for Biomechanics Research (BMEC), Mechanical and Biomedical Engineering, National University of Ireland, Galway, Ireland.
authors.forename: Ted J
authors.initials: TJ
authors.lastname: Vaughan
authors.affiliation: Centre for Biomechanics Research (BMEC), Mechanical and Biomedical Engineering, National University of Ireland, Galway, Ireland; National Centre for Biomedical Engineering Sciences (NCBES), National University of Ireland, Galway, Ireland. Electronic address: Laoise.McNamara@nuigalway.ie.
authors.forename: Laoise M
authors.initials: LM
authors.lastname: McNamara
mesh_terms: D000818:Animals; D015232:Dinoprostone / Q000378:metabolism; D005786:Gene Expression Regulation; D057446:Hydrodynamics; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D051379:Mice; D010011:Osteocytes / Q000166:cytology* / Q000378:metabolism*; D021381:Protein Transport; D013314:Stress, Mechanical
chemical_list: D039302:Integrin alphaVbeta3; D015232:Dinoprostone