Dose-response relationship between ambulatory load magnitude and load-induced changes in COMP in young healthy adults

Herger, Simon; Vach, Werner; Liphardt, Anna‐Maria; Egloff, Christian; Nüesch, Corina

doi:10.1016/j.joca.2018.09.002

Cited by 31 publications

(33 citation statements)

References 39 publications

(33 reference statements)

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“…Cheleschi et al [15] demonstrated a reduction of β-catenin protein expression in OA chondrocytes exposed to 3 h of low sinusoidal HP (1-5 MPa), while no consistent load-dependent changes in total or active β-catenin-levels were observed by Praxenthaler et al [69] after the application of a single dynamic compression-episode. In the present study, we partially confirm these results observing an increased β-catenin protein expression in OA chondrocytes upon application of a static continuous HP of 10 MPa, while its activation was limited in physiological HP-exposed cells (1)(2)(3)(4)(5). We further hypothesize that the effect of mechanical loading or, specifically, of HP on Wnt/β-catenin pathway could be mediated by miRNA.…”

Section: Discussionsupporting

confidence: 88%

“…Articular cartilage is constantly exposed to a wide range of static and dynamic cycles of loading that can vary from 0.7 to 20 MPa depending on body weight, posture, and physical activity [1][2][3]. Moderate loads are safe and contribute to maintain cartilage homeostasis and integrity, while excessive or static stresses could be deleterious, inducing its degradation, and contributing to the onset and the progression of osteoarthritis (OA) [4,5]. At the cellular level, a dynamic physiological compression promotes chondrocyte proliferation and activity, whereas injurious static stress induces opposing, detrimental effects on cell anabolism reducing the synthesis of extracellular matrix (ECM) components [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

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Hydrostatic Pressure Regulates Oxidative Stress through microRNA in Human Osteoarthritic Chondrocytes

Cheleschi

Barbarino

Gallo

et al. 2020

IJMS

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Hydrostatic pressure (HP) modulates chondrocytes metabolism, however, its ability to regulate oxidative stress and microRNAs (miRNA) has not been clarified. The aim of this study was to investigate the role of miR-34a, miR-146a, and miR-181a as possible mediators of HP effects on oxidative stress in human osteoarthritis (OA) chondrocytes. Chondrocytes were exposed to cyclic low HP (1–5 MPa) and continuous static HP (10 MPa) for 3~h. Metalloproteinases (MMPs), disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5, type II collagen (Col2a1), miR-34a, miR-146a, miR-181a, antioxidant enzymes, and B-cell lymphoma 2 (BCL2) were evaluated by quantitative real-time polymerase chain reaction qRT-PCR, apoptosis and reactive oxygen species ROS production by cytometry, and β-catenin by immunofluorescence. The relationship among HP, the studied miRNA, and oxidative stress was assessed by transfection with miRNA specific inhibitors. Low cyclical HP significantly reduced apoptosis, the gene expression of MMP-13, ADAMTS5, miRNA, the production of superoxide anion, and mRNA levels of antioxidant enzymes. Conversely, an increased Col2a1 and BCL2 genes was observed. β-catenin protein expression was reduced in cells exposed to HP 1–5 MPa. Opposite results were obtained following continuous static HP application. Finally, miRNA silencing enhanced low HP and suppressed continuous HP-induced effects. Our data suggest miRNA as one of the mechanisms by which HP regulates chondrocyte metabolism and oxidative stress, via Wnt/β-catenin pathway.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Hydrostatic Pressure Regulates Oxidative Stress through microRNA in Human Osteoarthritic Chondrocytes

Cheleschi

Barbarino

Gallo

et al. 2020

IJMS

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“…Research examining the effect of acute changes in body weight on sCOMP levels during walking exercise also suggest that catabolic activity occurs at a greater rate in loaded versus unloaded walking conditions (Denning et al, 2015). A more recent investigation examining healthy participants, also reports that increasing body weight by 20% (using a weighted vest) resulted in a significant increase in sCOMP levels after 30 minutes of walking exercise, as compared to exercise completed using 20% unweighted or normal body weight conditions (Herger et al, 2019).…”

Section: Introductionmentioning

confidence: 92%

The Effect of a Lower Body Positive Pressure Supported Treadmill Exercise Regime on Systemic Biomarkers of Inflammation and Cartilage Degradation in Individuals with Knee Osteoarthritis: A Pilot Study

Cornish

Peeler

2021

IJKSS

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Background: Knee osteoarthritis (OA) has been linked to a chronic low-grade inflammatory response and altered metabolic activity of articular cartilage. Objective: The purpose of this investigation was to evaluate the effectiveness of a 12-week (3 times/week) lower body positive pressure (LBPP) treadmill walking regime on knee pain and systemic biomarkers of inflammation and cartilage degradation. Methods: Sixteen overweight (BMI > 25 kg/m2) knee OA patients were randomized to a LBPP treadmill walking exercise group (N = 7) or non-exercise control group (N = 9). Baseline and 12-week follow-up assessments evaluated the following dependent variables: acute knee pain during full weight bearing treadmill walking; inflammatory biomarkers (C-reactive protein, interleukin-1β, interleukin-6, s100A8/A9, and tumor necrosis factor-α), and catabolic metabolism of articular cartilage (sCOMP). Results: Knee pain at baseline and follow-up remained unchanged for the non-exercise control group (P > 0.05). However, knee pain for the LBPP exercise group was significantly decreased at follow-up (P ≤ 0.05). No differences in the biomarkers of inflammation and cartilage degradation were observed for between and within group comparisons (all P > 0.05). Conclusions: Data suggested that the LBPP supported walking regime could be effectively used to promote regular weight bearing exercise without exacerbation of knee joint pain and did not increase levels of systemic inflammation or catabolic activity of articular cartilage in overweight knee OA patients. This pilot investigation offers important insight regarding the potential role that the LBPP technology could play in facilitating investigations examining the disease modifying effect of exercise on knee OA pathogenesis.

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“…MMP serum levels are usually low in healthy individuals and increasing levels have been reported in arthritic patients 28 . Serum concentrations of MMP‐1, MMP‐3, and MMP‐9 are sensitive to loading with increasing values after, for example, resistive exercise (MMP‐1), 29 walking (MMP‐3 only), half‐marathon, marathon, and ultra‐marathon running 30‐32 . The expression of MMPs is usually regulated by cytokines such as tumor necrosis factor‐alpha (TNF‐α) which can be elevated after exercise 33 .…”

Section: Introductionmentioning

confidence: 99%

“…28 Serum concentrations of MMP-1, MMP-3, and MMP-9 are sensitive to loading with increasing values after, for example, resistive exercise (MMP-1), 29 walking (MMP-3 only), half-marathon, marathon, and ultra-marathon running. [30][31][32] The expression of MMPs is usually regulated by cytokines such as tumor necrosis factor-alpha (TNF-α) which can be elevated after exercise. 33 Leong et al 34 reported an increase in MMP-3 messenger RNA (mRNA) expression as early as 6 hours after immobilization using hind-limb unloading in rats followed by increased enzyme activity starting after 1 day of immobilization and both lasting until 21 days of immobilization.…”

mentioning

confidence: 99%

Locomotion replacement exercise cannot counteract cartilage biomarker response to 5 days of immobilization in healthy adults

Liphardt

Mündermann

Heer

et al. 2020

Journal Orthopaedic Research

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Biomarkers of cartilage metabolism are sensitive to changes in the biological and mechanical environment and can indicate early changes in cartilage homeostasis. The purpose of this study was to determine if a daily locomotion replacement program can serve as a countermeasure for changes in cartilage biomarker serum concentration caused by immobilization. Ten healthy male subjects (mean ± 1 standard deviation; age: 29.4 ± 5.9 years; body mass: 77.7 ± 4.1 kg) participated in the crossover 5-day bed rest study with three interventions: control (CON), standing (STA), and locomotion replacement training (LRT). Serum samples were taken before, during, and after bed rest. Biomarker concentrations were measured using commercial enzyme-linked immunosorbent assays. Cartilage oligomeric matrix protein (COMP) levels after 24 hours of bed rest decreased independently of the intervention (−16.8% to −9.8%) and continued to decrease until 72 hours of bed rest (minimum, −23.2% to −20.6%). LRT and STA did not affect COMP during bed rests (P = .056) but there was a strong tendency for a slower decrease with LRT (−9.4%)

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Dose-response relationship between ambulatory load magnitude and load-induced changes in COMP in young healthy adults

Cited by 31 publications

References 39 publications

Hydrostatic Pressure Regulates Oxidative Stress through microRNA in Human Osteoarthritic Chondrocytes

Hydrostatic Pressure Regulates Oxidative Stress through microRNA in Human Osteoarthritic Chondrocytes

The Effect of a Lower Body Positive Pressure Supported Treadmill Exercise Regime on Systemic Biomarkers of Inflammation and Cartilage Degradation in Individuals with Knee Osteoarthritis: A Pilot Study

Locomotion replacement exercise cannot counteract cartilage biomarker response to 5 days of immobilization in healthy adults

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