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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 653-662 |
| Number of pages | 10 |
| Journal | Journal of Orthopaedic Research |
| Volume | 36 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2018 |
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Keywords
- bone
- cell wounding
- mechanical loading
- mechanotransduction
- osteocyte
- skeleton
ASJC Scopus subject areas
- Orthopedics and Sports Medicine
Cite this
Mechanical loading disrupts osteocyte plasma membranes which initiates mechanosensation events in bone. / Yu, Kanglun; Sellman, David P.; Bahraini, Anoosh; Hagan, Mackenzie L.; Elsherbini, Ahmed; Vanpelt, Kayce T.; Marshall, Peyton L.; Hamrick, Mark W; McNeil, Anna; McNeil, Paul L; McGee Lawrence, Meghan Elizabeth.
In: Journal of Orthopaedic Research, Vol. 36, No. 2, 01.02.2018, p. 653-662.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mechanical loading disrupts osteocyte plasma membranes which initiates mechanosensation events in bone
AU - Yu, Kanglun
AU - Sellman, David P.
AU - Bahraini, Anoosh
AU - Hagan, Mackenzie L.
AU - Elsherbini, Ahmed
AU - Vanpelt, Kayce T.
AU - Marshall, Peyton L.
AU - Hamrick, Mark W
AU - McNeil, Anna
AU - McNeil, Paul L
AU - McGee Lawrence, Meghan Elizabeth
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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.
KW - bone
KW - cell wounding
KW - mechanical loading
KW - mechanotransduction
KW - osteocyte
KW - skeleton
UR - http://www.scopus.com/inward/record.url?scp=85042938845&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042938845&partnerID=8YFLogxK
U2 - 10.1002/jor.23665
DO - 10.1002/jor.23665
M3 - Article
VL - 36
SP - 653
EP - 662
JO - Journal of Orthopaedic Research
JF - Journal of Orthopaedic Research
SN - 0736-0266
IS - 2
ER -