Mechanical loading highly increases IL-6 production and decreases OPG expression by osteoblasts

Sanchez, Christelle; Gabay, Odile; Salvat, Colette; Henrotin, Yves; Bérenbaum, Francis

doi:10.1016/j.joca.2008.09.007

Cited by 128 publications

(124 citation statements)

References 47 publications

Supporting

Mentioning

108

Contrasting

Unclassified

Order By: Relevance

“…In fact, previous gene expression studies of cells subjected to large mechanical loads have reported regulation of stress and inflammatory genes. 15,35,36 In comparison, there were no signs of upregulation of inflammatory or stressrelated genes in the present study, supporting the suggestion of an appropriate level of strain being utilized. Our study also showed a markedly lower total number of changes in gene expression in response to a mechanical loading.…”

Section: Discussionsupporting

confidence: 83%

“…Commonly a gel based scaffold or tissue culture plastic has been used as the substrate on which cells were mechanically loaded, and the strain employed has been in the range of 2%-20%. 6,[12][13][14][15][16][17][18][19][20] Neither the scaffold nor the strain of this magnitude represents the true environment or magnitude of physiological or pathological loading of bone in humans in vivo. Further, a number of studies in vivo have been carried out in an attempt to overcome these obstacles, but these are limited to animal models and therefore could be associated with differences in responses to loading and mechanisms involved from one species to another.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Gene Expression Responses to Mechanical Stimulation of Mesenchymal Stem Cells Seeded on Calcium Phosphate Cement

Gharibi

Cama

Capurro

et al. 2013

Tissue Engineering Part A

View full text Add to dashboard Cite

Introduction: The aim of the study reported here was to investigate the molecular responses of human mesenchymal stem cells (MSC) to loading with a model that attempts to closely mimic the physiological mechanical loading of bone, using monetite calcium phosphate (CaP) scaffolds to mimic the biomechanical properties of bone and a bioreactor to induce appropriate load and strain. Methods: Human MSCs were seeded onto CaP scaffolds and subjected to a pulsating compressive force of 5.5 -4.5 N at a frequency of 0.1 Hz. Early molecular responses to mechanical loading were assessed by microarray and quantitative reverse transcription-polymerase chain reaction and activation of signal transduction cascades was evaluated by western blotting analysis. Results: The maximum mechanical strain on cell/scaffolds was calculated at around 0.4%. After 2 h of loading, a total of 100 genes were differentially expressed. The largest cluster of genes activated with 2 h stimulation was the regulator of transcription, and it included FOSB. There were also changes in genes involved in cell cycle and regulation of protein kinase cascades. When cells were rested for 6 h after mechanical stimulation, gene expression returned to normal. Further resting for a total of 22 h induced upregulation of 63 totally distinct genes that were mainly involved in cell surface receptor signal transduction and regulation of metabolic and cell division processes. In addition, the osteogenic transcription factor RUNX-2 was upregulated. Twenty-four hours of persistent loading also markedly induced osterix expression. Mechanical loading resulted in upregulation of Erk1/2 phosphorylation and the gene expression study identified a number of possible genes (SPRY2, RIPK1, SPRED2, SERTAD1, TRIB1, and RAPGEF2) that may regulate this process. Conclusion:The results suggest that mechanical loading activates a small number of immediate-early response genes that are mainly associated with transcriptional regulation, which subsequently results in activation of a wider group of genes including those associated with osteoblast proliferation and differentiation. The results provide a valuable insight into molecular events and signal transduction pathways involved in the regulation of MSC osteogenic differentiation in response to a physiological level of mechanical stimulation.

show abstract

Section: Discussionsupporting

confidence: 83%

mentioning

confidence: 99%

Gene Expression Responses to Mechanical Stimulation of Mesenchymal Stem Cells Seeded on Calcium Phosphate Cement

Gharibi

Cama

Capurro

et al. 2013

Tissue Engineering Part A

View full text Add to dashboard Cite

show abstract

“…In mechanobiological studies, different culture systems and mechanical forces are used for cellular stimulation. Compressive forces, tensile strain, hydrostatic pressure, and shear forces are frequently used as biomechanical stimuli [21][22][23][24]. A well-established device for application of tensile strain was used in our study [17].…”

Section: Discussionmentioning

confidence: 99%

Regulation of gene expression in articular cells is influenced by biomechanical loading

Rath¹,

Springorum

Deschner

et al. 2012

Open Medicine

View full text Add to dashboard Cite

show abstract

“…2 Although it is impossible to detect the change in bone remodeling on plain radiography alone, magnetic resonance imaging (MRI) and bone scintigraphy have been adopted for this purpose. 3 In our department, we adopted positron emission tomography (PET) for the evaluation of patients with early or pre-osteoarthritis of the hip, and our previous study suggested the usefulness of 18 F-fluoride PET for the early detection of hip osteoarthritis. 4 One question is: what causes bone remodeling acceleration in early stage osteoarthritis?…”

mentioning

confidence: 99%

“…Our hypothesis is that mechanical stress concentration in the hip joint may be related to bone remodeling abnormalities. The purpose of this study was therefore to examine the relationship between mechanical stress distribution calculated by finite element analysis (FEA) and 18 F-fluoride PET uptake in the hip joint.…”

mentioning

confidence: 99%

Correlation between mechanical stress by finite element analysis and ¹⁸F‐fluoride PET uptake in hip osteoarthritis patients

Hirata

Inaba²,

Kobayashi³

et al. 2014

Journal Orthopaedic Research

View full text Add to dashboard Cite

ABSTRACT:18 F-fluoride positron emission tomography ( 18 F-fluoride PET) is a functional imaging modality used primarily to detect increased bone metabolism. Increased 18 F-fluoride PET uptake suggests an association between increased bone metabolism and load stress at the subchondral level. This study therefore examined the relationship between equivalent stress distribution calculated by finite element analysis and 18 F-fluoride PET uptake in patients with hip osteoarthritis. The study examined 34 hips of 17 patients who presented to our clinic with hip pain, and were diagnosed with osteoarthritis or pre-osteoarthritis. The hips with trauma, infection, or bone metastasis of cancer were excluded. Three-dimensional models of each hip were created from computed tomography data to calculate the maximum equivalent stress by finite element analysis, which was compared with the maximum standardized uptake value (SUV max ) examined by 18 F-fluoride PET. The SUV max and equivalent stress were correlated (Spearman's rank correlation coefficient r ¼ 0.752), and higher equivalent stress values were noted in higher SUV max patients. The correlation between SUV max and maximum equivalent stress in osteoarthritic hips suggests the possibility that 18 F-fluoride PET detect increased bone metabolism at sites of stress concentration. This study demonstrates the correlation between mechanical stress and bone remodeling acceleration in hip osteoarthritis. ß

show abstract

Mechanical loading highly increases IL-6 production and decreases OPG expression by osteoblasts

Abstract: This work demonstrates that IL-6 is mechano-sensitive cytokine and probably a key factor in the biomechanical control of bone remodeling in OA.

Cited by 128 publications

References 47 publications

Gene Expression Responses to Mechanical Stimulation of Mesenchymal Stem Cells Seeded on Calcium Phosphate Cement

Gene Expression Responses to Mechanical Stimulation of Mesenchymal Stem Cells Seeded on Calcium Phosphate Cement

Regulation of gene expression in articular cells is influenced by biomechanical loading

Correlation between mechanical stress by finite element analysis and ¹⁸F‐fluoride PET uptake in hip osteoarthritis patients

Contact Info

Product

Resources

About

Mechanical loading highly increases IL-6 production and decreases OPG expression by osteoblasts

Abstract: This work demonstrates that IL-6 is mechano-sensitive cytokine and probably a key factor in the biomechanical control of bone remodeling in OA.

Cited by 128 publications

References 47 publications

Gene Expression Responses to Mechanical Stimulation of Mesenchymal Stem Cells Seeded on Calcium Phosphate Cement

Gene Expression Responses to Mechanical Stimulation of Mesenchymal Stem Cells Seeded on Calcium Phosphate Cement

Regulation of gene expression in articular cells is influenced by biomechanical loading

Correlation between mechanical stress by finite element analysis and 18F‐fluoride PET uptake in hip osteoarthritis patients

Contact Info

Product

Resources

About

Correlation between mechanical stress by finite element analysis and ¹⁸F‐fluoride PET uptake in hip osteoarthritis patients