@article{129df4e6d58d42ee8f21cad0a804c967,
title = "Mechanical loading disrupts osteocyte plasma membranes which initiates mechanosensation events in bone",
abstract = "Osteocytes sense loading in bone, but their mechanosensation mechanisms remain poorly understood. Plasma membrane disruptions (PMD) develop with loading under physiological conditions in many cell types (e.g., myocytes, endothelial cells). These PMD foster molecular flux across cell membranes that promotes tissue adaptation, but this mechanosensation mechanism had not been explored in osteocytes. Our goal was to investigate whether PMD occur and initiate consequent mechanotransduction in osteocytes during physiological loading. We found that osteocytes experience PMD during in vitro (fluid flow) and in vivo (treadmill exercise) mechanical loading, in proportion to the level of stress experienced. In fluid flow studies, osteocyte PMD preferentially formed with rapid as compared to gradual application of loading. In treadmill studies, osteocyte PMD increased with loading in weight bearing locations (tibia), but this trend was not seen in non-weight bearing locations (skull). PMD initiated osteocyte mechanotransduction including calcium signaling and expression of c-fos, and repair rates of these PMD could be enhanced or inhibited pharmacologically to alter downstream mechanotransduction and osteocyte survival. PMD may represent a novel mechanosensation pathway in bone and a target for modifying skeletal adaptation signaling in osteocytes.",
keywords = "bone, cell wounding, mechanical loading, mechanotransduction, osteocyte, skeleton",
author = "Kanglun Yu and Sellman, {David P.} and Anoosh Bahraini and Hagan, {Mackenzie L.} and Ahmed Elsherbini and Vanpelt, {Kayce T.} and Marshall, {Peyton L.} and Hamrick, {Mark W} and Anna McNeil and McNeil, {Paul L} and {McGee Lawrence}, {Meghan Elizabeth}",
note = "Funding Information: Funding was received from the National Science Foundation (CMMI 1727949), the National Institute on Aging (P01 AG036675), the Medical College of Georgia at Augusta University, the Augusta University Medical Scholars Program, and the Augusta University Student Training and Research (STAR) Program. The authors wish to thank Mr. Tim Kurtz and the Augusta University Cell Imaging Core Laboratory for assistance with imaging procedures and Drs. Mohammed Elsalanty and Regina Messer for assistance with the fluid flow studies. Funding Information: Conflicts of interest: None. Grant sponsor: National Science Foundation, Division of Civil, Mechanical and Manufacturing Innovation; Grant number: CMMI 1727949; Grant sponsor: National Institute on Aging; Grant number: P01 AG036675; Grant sponsor: Medical College of Georgia at Augusta University; Grant sponsor: Augusta University Medical Scholars Program; Grant sponsor: Augusta University Student Training and Research (STAR) Program. Correspondence to: Meghan E. McGee-Lawrence (T: (706) 446-0128; F: (706) 721-6120; E-mail: mmcgeelawrence@augusta.edu) Publisher Copyright: {\textcopyright} 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.",
year = "2018",
month = feb,
doi = "10.1002/jor.23665",
language = "English (US)",
volume = "36",
pages = "653--662",
journal = "Journal of Orthopaedic Research",
issn = "0736-0266",
publisher = "John Wiley and Sons Inc.",
number = "2",
}