Substrate Deformation Levels Associated With Routine Physical Activity Are Less Stimulatory to Bone Cells Relative to Loading-Induced Oscillatory Fluid Flow

You, Jun; Yellowley, Clare E.; Donahue, Henry J.; Zhang, Y.; Chen, Q.; Jacobs, Christopher R.

doi:10.1115/1.1287161

Cited by 318 publications

(257 citation statements)

References 39 publications

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“…Note that the fluid flow to which osteocytes were exposed in this study is 2 hours. Several others studies (1,16,50,51,57) have shown that mechanical stimuli at this duration can induce many changes in markers of bone formation/resorption in bone cells. We expect that with longer flow exposure times, the bone resorption inhibition effect from mechanical loading might be further enhanced.…”

Section: Discussionmentioning

confidence: 99%

“…Dynamic fluid flow is one of the mechanical stimuli that osteocytes experience in vivo with habitual loading (24,25,54). Previous studies have established that this loading-induced dynamic fluid flow is a potent physical signal in the regulation of bone cell metabolism (7,16,37,57), yet it is unclear what role it might play in osteocyte mediated regulation of bone resorption.…”

Section: Introductionmentioning

confidence: 99%

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

You

Temiyasathit

Lee

et al. 2008

Bone

289

156

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

You

Temiyasathit

Lee

et al. 2008

Bone

289

156

View full text Add to dashboard Cite

show abstract

“…Previous in vitro cell culture studies have established 10,000 µε in bone cells as a threshold above which an osteogenic response is stimulated (Burger and Veldhuijzen 1993b;You et al 2000). In order to determine whether changes in strain observed in our previous experimental study (Verbruggen et al 2015) could explore the possible mechanical properties in the computational model that could predict the observed experimental results.…”

Section: Parameter Variation Study Of Elastic Modulimentioning

confidence: 98%

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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“…It has been hypothesized that bone remodeling is controlled at the cellular level through signals mediated by osteocytes [25]. This hypothesis has been supported by results from in vitro experiments by You et al [26,27] in which bone cells were subjected to a fluid flow generated by shear stresses. The results of an in vivo experimental study by Vashishth et al [28] support the sensory role of osteocytes in human cortical bone and the decline of the osteocyte lacunar density caused by an accumulation of microcracks.…”

Section: Model Based On Ruptured Osteocyte Processes (Roc)mentioning

confidence: 95%

A theory for bone resorption based on the local rupture of osteocytes cells connections: A finite element study

Hambli

Almitani

Chamekh

et al. 2015

Mathematical Biosciences

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In this work, a bone damage resorption finite element model based on the disruption of the inhibitory signal transmitted between osteocytes cells in bone due to damage accumulation is developed and discussed. A strain-based stimulus function coupled to a damage-dependent spatial function is proposed to represent the connection between two osteocytes embedded in the bone tissue. The signal is transmitted to the bone surface to activate bone resorption. The proposed model is based on the idea that the osteocyte signal reduction is not related to the reduction of the stimulus sensed locally by osteocytes due to damage, but to the difficulties for the signal in travelling along a disrupted area due to microcracks that can destroy connections of the intercellular network between osteocytes and bone-lining cells. To check the potential of the proposed model to predict the damage resorption process, two bone resorption mechano-regulation rules corresponding to two mechanotransduction approaches have been implemented and tested: 1) Bone resorption based on a coupled strain-damage stimulus function without ruptured osteocyte connections (NROC); and 2) Bone resorption based on a strain stimulus function with ruptured osteocyte connections (ROC).The comparison between the results obtained by both models, shows that the proposed model based on ruptured osteocytes connections predicts realistic results in conformity with previously published findings concerning the fatigue damage repair in bone.

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Substrate Deformation Levels Associated With Routine Physical Activity Are Less Stimulatory to Bone Cells Relative to Loading-Induced Oscillatory Fluid Flow

Cited by 318 publications

References 39 publications

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

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

Mechanisms of osteocyte stimulation in osteoporosis

A theory for bone resorption based on the local rupture of osteocytes cells connections: A finite element study

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