Fluoride inhibits the response of bone cells to mechanical loading

Willems, Hubertine M. E.; Heuvel, Ellen G. H. M. van den; Castelein, Seb; Buisman, Joost Keverling; Bronckers, A.L.J.J.; Bakker, Astrid D.; Klein‐Nulend, Jenneke

doi:10.1007/s10266-011-0013-6

Cited by 8 publications

(4 citation statements)

References 27 publications

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“…The actin measurements were conducted in light of the known effects of mTORc2 on actin cytoskeleton reorganization. As the osteocyte actin cytoskeleton is purported to modulate mechanosensitivity in both computational (32) and experimental (33,34) models, the deficit in mechanotransduction induced by Rictor mutation is consistent with our measurements, indicating that cytoskeletal integrity is disrupted. However, we cannot rule out the possibility that Rictor controls mechanotransduction by other, yet undescribed, signal transduction mechanisms.…”

Section: Discussionsupporting

confidence: 87%

The mTORC2 Component Rictor Is Required for Load‐Induced Bone Formation in Late‐Stage Skeletal Cells

Lewis

Wright

et al. 2020

JBMR Plus

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Bone relies on mechanical cues to build and maintain tissue composition and architecture. Our understanding of bone cell mechanotransduction continues to evolve, with a few key signaling pathways emerging as vital. Wnt/β-catenin, for example, is essential for proper anabolic response to mechanical stimulation. One key complex that regulates β-catenin activity is the mammalian target of rapamycin complex 2 (mTORc2). mTORc2 is critical for actin cytoskeletal reorganization, an indispensable component in mechanotransduction in certain cell types. In this study, we probed the impact of the mTORc2 signaling pathway in osteocyte mechanotransduction by conditionally deleting the mTORc2 subunit Rictor in Dmp1-expressing cells of C57BL/6 mice. Conditional deletion of the Rictor was achieved using the Dmp1-Cre driver to recombine Rictor floxed alleles. Rictor mutants exhibited a decrease in skeletal properties, as measured by DXA, μCT, and mechanical testing, compared with Cre-negative floxed littermate controls. in vivo axial tibia loading conducted in adult mice revealed a deficiency in the osteogenic response to loading among Rictor mutants. Histological measurements of osteocyte morphology indicated fewer, shorter cell processes in Rictor mutants, which might explain the compromised response to mechanical stimulation. In summary, inhibition of the mTORc2 pathway in late osteoblasts/osteocytes leads to decreased bone mass and mechanically induced bone formation.

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Section: Discussionsupporting

confidence: 87%

The mTORC2 Component Rictor Is Required for Load‐Induced Bone Formation in Late‐Stage Skeletal Cells

Lewis

Wright

et al. 2020

JBMR Plus

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“…High-dose fluoride-induced inhibition of osteoblast viability may also be associated with MAPK-mediated Yes-associated protein (YAP) activation [ 237 ]. Fluoride also inhibited osteocyte response to mechanical loading due to cytoskeletal alterations [ 238 ].…”

Section: Fluoride (F)mentioning

confidence: 99%

The Role of Trace Elements and Minerals in Osteoporosis: A Review of Epidemiological and Laboratory Findings

et al. 2023

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The objective of the present study was to review recent epidemiological and clinical data on the association between selected minerals and trace elements and osteoporosis, as well as to discuss the molecular mechanisms underlying these associations. We have performed a search in the PubMed-Medline and Google Scholar databases using the MeSH terms “osteoporosis”, “osteogenesis”, “osteoblast”, “osteoclast”, and “osteocyte” in association with the names of particular trace elements and minerals through 21 March 2023. The data demonstrate that physiological and nutritional levels of trace elements and minerals promote osteogenic differentiation through the up-regulation of BMP-2 and Wnt/β-catenin signaling, as well as other pathways. miRNA and epigenetic effects were also involved in the regulation of the osteogenic effects of trace minerals. The antiresorptive effect of trace elements and minerals was associated with the inhibition of osteoclastogenesis. At the same time, the effect of trace elements and minerals on bone health appeared to be dose-dependent with low doses promoting an osteogenic effect, whereas high doses exerted opposite effects which promoted bone resorption and impaired bone formation. Concomitant with the results of the laboratory studies, several clinical trials and epidemiological studies demonstrated that supplementation with Zn, Mg, F, and Sr may improve bone quality, thus inducing antiosteoporotic effects.

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“…This is best accomplished by the cytoskeleton, which connects the integrins, cadherins and primary cilium in the cell membrane to the nucleus [ 93 ]. Indeed, it is well established that disrupting the cytoskeleton eliminates mechanosensing in osteocytes [ 94 ]. One of the earliest models explicitly considering the cytoskeleton was presented by McGarry [ 95 ].…”

Section: Finite Element Models Of Single Cellsmentioning

confidence: 99%

Finite Element Models of Osteocytes and Their Load-Induced Activation

Smit

2022

Curr Osteoporos Rep

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Purpose of Review Osteocytes are the conductors of bone adaptation and remodelling. Buried inside the calcified matrix, they sense mechanical cues and signal osteoclasts in case of low activity, and osteoblasts when stresses are high. How do osteocytes detect mechanical stress? What physical signal do they perceive? Finite element analysis is a useful tool to address these questions as it allows calculating stresses, strains and fluid flow where they cannot be measured. The purpose of this review is to evaluate the capabilities and challenges of finite element models of bone, in particular the osteocytes and load-induced activation mechanisms. Recent Findings High-resolution imaging and increased computational power allow ever more detailed modelling of osteocytes, either in isolation or embedded within the mineralised matrix. Over the years, homogeneous models of bone and osteocytes got replaced by heterogeneous and microstructural models, including, e.g. the lacuno-canalicular network and the cytoskeleton. Summary The lacuno-canalicular network induces strain amplifications and the osteocyte protrusions seem to be stimulated much more than the cell body, both by strain and fluid flow. More realistic cell geometries, like minute constrictions of the canaliculi, increase this effect. Microstructural osteocyte models describe the transduction of external stimuli to the nucleus. Supracellular multiscale models (e.g. of a tunnelling osteon) allow to study differential loading of osteocytes and to distinguish between strain and fluid flow as the pivotal stimulatory cue. In the future, the finite element models may be enhanced by including chemical transport and intercellular communication between osteocytes, osteoclasts and osteoblasts.

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Fluoride inhibits the response of bone cells to mechanical loading

Cited by 8 publications

References 27 publications

The mTORC2 Component Rictor Is Required for Load‐Induced Bone Formation in Late‐Stage Skeletal Cells

The mTORC2 Component Rictor Is Required for Load‐Induced Bone Formation in Late‐Stage Skeletal Cells

The Role of Trace Elements and Minerals in Osteoporosis: A Review of Epidemiological and Laboratory Findings

Finite Element Models of Osteocytes and Their Load-Induced Activation

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