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Abstract Transient plasma membrane disruptions (PMD) occur in osteocytes with in vitro and in vivo loading, initiating mechanotransduction. The goal here was to determine whether osteocyte PMD formation or repair is affected by aging. Osteocytes from old (24 months) mice developed fewer PMD (−76% females, −54% males) from fluid shear than young (3 months) mice, and old mice developed fewer osteocyte PMD (−51%) during treadmill running. This was due at least in part to decreased pericellular matrix production, as studies revealed that pericellular matrix is integral to formation of osteocyte PMD, and aged osteocytes produced less pericellular matrix (−55%). Surprisingly, osteocyte PMD repair rate was faster (+25% females, +26% males) in osteocytes from old mice, and calcium wave propagation to adjacent nonwounded osteocytes was blunted, consistent with impaired mechanotransduction downstream of PMD in osteocytes with fast PMD repair in previous studies. Inducing PMD via fluid flow in young osteocytes in the presence of oxidative stress decreased postwounding cell survival and promoted accelerated PMD repair in surviving cells, suggesting selective loss of slower‐repairing osteocytes. Therefore, as oxidative stress increases during aging, slower‐repairing osteocytes may be unable to successfully repair PMD, leading to slower‐repairing osteocyte death in favor of faster‐repairing osteocyte survival. Since PMD are an important initiator of mechanotransduction, age‐related decreases in pericellular matrix and loss of slower‐repairing osteocytes may impair the ability of bone to properly respond to mechanical loading with bone formation. These data suggest that PMD formation and repair mechanisms represent new targets for improving bone mechanosensitivity with aging.
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Modeling and simulation of osteocyte process–fluid interaction in a canaliculus
An osteocyte is a bone cell situated inside a hard bone matrix in an interstice (lacuna). It has many dendritic structures called cellular processes that radiate outward from the cell through the bone matrix via cylindrical openings (canaliculi). Osteocytes can sense stress and strain applied by the interstitial fluid flow and respond by releasing biochemical signals that regulate bone remodeling. In vitro experiments have suggested that the stress and strain typically experienced at the macroscale tissue level have to be amplified 10× in order for osteocytes to have a significant response in vivo. This stress and strain amplification mechanism is not yet well understood. Previous studies suggest that the processes are the primary sites for mechanosensation thanks to the tethering elements that attach the process membrane to the canalicular wall. However, there are other potential factors which may also contribute to stress and strain amplification, such as canalicular wall geometry and osteocyte-associated proteins in the interstitial space called pericellular matrix. In this work, we perform computational studies to study how canalicular wall roughness affects stress and strain amplification. Our major finding is that the wall roughness induces significantly greater wall shear stress (WSS) on the process when the wall roughness increases flow resistance; and the roughness has relatively smaller influence on the WSS when the resistance remains the same.
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- Award ID(s):
- 1951531
- PAR ID:
- 10589124
- Publisher / Repository:
- American Institute of Physics
- Date Published:
- Journal Name:
- Physics of Fluids
- Volume:
- 36
- Issue:
- 6
- ISSN:
- 1070-6631
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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