A model for strain amplification in the actin cytoskeleton of osteocytes due to fluid drag on pericellular matrix

You, Lidan; Cowin, Stephen C.; Schaffler, Mitchell B.; Weinbaum, Sheldon

doi:10.1016/s0021-9290(01)00107-5

Cited by 360 publications

(358 citation statements)

References 47 publications

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“…For example, accelerations may generate drag forces that perturb osteocytic processes in the pericellular matrix, 41 providing a strong amplification mechanism for even very small mechanical events. 42 However, cells might respond to vibrations even in absence of their native environment in vitro, 43,44 perhaps modulated by oscillations of the nucleus in the cytoplasm. 45 Nevertheless, a generic cell response to vibrations is inconsistent with the sitespecific responses observed here, and mechanical factors could interact with physiological (e.g., altered blood flow [46][47][48] ) and cellular (e.g., cell communication 49 ) factors to define the tissue-level response.…”

Section: Discussionmentioning

confidence: 99%

Low‐level accelerations applied in the absence of weight bearing can enhance trabecular bone formation

Garman

Gaudette

Donahue

et al. 2007

Journal Orthopaedic Research

138

134

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High-frequency whole body vibrations can be osteogenic, but their efficacy appears limited to skeletal segments that are weight bearing and thus subject to the induced load. To determine the anabolic component of this signal, we investigated whether low-level oscillatory displacements, in the absence of weight bearing, are anabolic to skeletal tissue. A loading apparatus, developed to shake specific segments of the murine skeleton without the direct application of deformations to the tissue, was used to subject the left tibia of eight anesthesized adult female C57BL/6J mice to small (0.3 g or 0.6 g) 45 Hz sinusoidal accelerations for 10 min/day, while the right tibia served as an internal control. Video and strain analysis revealed that motions of the apparatus and tibia were well coupled, inducing dynamic cortical deformations of less than three microstrain. After 3 weeks, trabecular metaphyseal bone formation rates and the percentage of mineralizing surfaces (MS/BS) were 88% and 64% greater (p < 0.05) in tibiae accelerated at 0.3 g than in their contralateral controls. At 0.6 g, bone formation rates and mineral apposition rates were 66% and 22% greater (p < 0.05) in accelerated tibiae. Changes in bone morphology were evident only in the epiphysis, where stimulated tibiae displayed significantly greater cortical area (þ8%) and thickness (þ8%). These results suggest that tiny acceleratory motions -independent of direct loading of the matrix -can influence bone formation and bone morphology. If confirmed by clinical studies, the unique nature of the signal may ultimately facilitate the stimulation of skeletal regions that are prone to osteoporosis even in patients that are suffering from confinement to wheelchairs, bed rest, or space travel. ß

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Section: Discussionmentioning

confidence: 99%

Low‐level accelerations applied in the absence of weight bearing can enhance trabecular bone formation

Garman

Gaudette

Donahue

et al. 2007

Journal Orthopaedic Research

138

134

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“…Previous studies have investigated the role of proteoglycan PCM elements, which tether the osteocyte to the surrounding extracellular matrix (Han et al 2004;You et al 2004;You et al 2001), and projections of the ECM into the canaliculi, which disturb the flow or attach directly to the cell process via integrin attachments (Anderson and Knothe Tate 2008;McNamara et al 2009;Wang et al 2007). To date no computational approach has been capable of modelling this complex multi-physics behaviour, incorporating both mechanisms into a full scale model of the osteocyte.…”

Section: Fsi Model Generationmentioning

confidence: 99%

Mechanisms of osteocyte stimulation in osteoporosis

Verbruggen

Vaughan

McNamara

2016

Journal of the Mechanical Behavior of Biomedical Materials

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Experimental studies have shown that primary osteoporosis caused by oestrogen-deficiency results in localised alterations in bone tissue properties and mineral composition. Additionally, changes to the lacunar-canalicular architecture surrounding the mechanosensitive osteocyte have been observed in animal models of the disease. Recently, it has also been demonstrated that the mechanical stimulation sensed by osteocytes changes significantly during osteoporosis.Specifically, it was shown osteoporotic bone cells experience higher maximum strains than healthy bone cells after short durations of oestrogen deficiency. However, in long-term oestrogen deficiency there was no significant difference between bone cells in healthy and normal bone. The mechanisms by which these changes arise are unknown. In this study, we test the hypothesis that complex changes in tissue composition and lacunar-canalicular architecture during osteoporosis alter the mechanical stimulation of the osteocyte. The objective of this research is to employ computational methods to investigate the relationship between changes in bone tissue composition and microstructure and the mechanical stimulation of osteocytes during osteoporosis. By simulating physiological loading, it was observed that an initial decrease in tissue stiffness (of 0.425 GPa) and mineral content (of 0.66 wt% Ca) relative to controls could explain the mechanical stimulation observed at the early stages of oestrogen deficiency (5 weeks post-OVX) during in situ bone cell loading in an oestrogendeficient rat model of post-menopausal osteoporosis (Verbruggen et al. 2015). Moreover, it was found that a later increase in stiffness (of 1.175 GPa) and mineral content (of 1.64 wt% Ca) during long-term osteoporosis (34 weeks post-OVX), could explain the mechanical stimuli previously observed at a later time point due to the progression of osteoporosis. Furthermore, changes in canalicular tortuosity arising during osteoporosis were shown to result in increased osteogenic strain stimulation, though to a lesser extent than has been observed experimentally.The findings of this study indicate that changes in the extracellular environment during osteoporosis, arising from altered mineralisation and lacunar-canalicular architecture, lead to altered mechanical stimulation of osteocytes, and provide an enhanced understanding of changes in bone mechanobiology during osteoporosis.

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“…These fluid-filled lacunae and canaliculi also contain a proteoglycan-rich extracellular matrix which affects the diffusion of soluble factors released by osteocytes. Two key features of osteocytes as mechanosensors are their ability to detect mechanical stimuli and to send signals to other effector cells that regulate bone formation and resorption (5,6,56,58,59). Dynamic fluid flow is one of the mechanical stimuli that osteocytes experience in vivo with habitual loading (24,25,54).…”

Section: Introductionmentioning

confidence: 99%

Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading

You

Temiyasathit

Lee

et al. 2008

Bone

Self Cite

285

148

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Bone has the ability to adjust its structure to meet its mechanical environment. The prevailing view of bone mechanobiology is that osteocytes are responsible for detecting and responding to mechanical loading and initiating the bone adaptation process. However, how osteocytes signal effector cells and initiate bone turnover is not well understood. Recent in vitro studies have shown that osteocytes support osteoclast formation and activation when co-cultured with osteoclast precursors. In this study, we examined the osteocytes' role in the mechanical regulation of osteoclast formation and activation.We demonstrated here that 1) Mechanical stimulation of MLO-Y4 osteocyte-like cells decreases their osteoclastogenic-support potential when co-cultured with RAW264.7 monocyte osteoclast precursors, 2) Soluble factors released by these mechanically stimulated MLO-Y4 cells inhibit osteoclastogenesis induced by ST2 bone marrow stromal cells or MLO-Y4 cells, and 3) Soluble RANKL and OPG were released by MLO-Y4 cells, and the expressions of both were found to be mechanically regulated.Our data suggests that mechanical loading decreases the osteocyte's potential to induce osteoclast formation by direct cell-cell contact. However, it is not clear that osteocytes in vivo are able to form contacts with osteoclast precursors. Our data also demonstrates that mechanically stimulated osteocytes release soluble factors that can inhibit osteoclastogenesis induced by other supporting

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A model for strain amplification in the actin cytoskeleton of osteocytes due to fluid drag on pericellular matrix

Cited by 360 publications

References 47 publications

Low‐level accelerations applied in the absence of weight bearing can enhance trabecular bone formation

Low‐level accelerations applied in the absence of weight bearing can enhance trabecular bone formation

Mechanisms of osteocyte stimulation in osteoporosis

Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading

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