Does moderate intensity impact exercise and non-impact exercise induce acute changes in collagen biochemical markers related to osteoarthritis? – An exploratory randomized cross-over trial

Bjerre-Bastos, J.J.; Nielsen, Henning Bay; Andersen, J.R.; Karsdal, Morten A.; Bay‐Jensen, Anne‐Christine; Boesen, Magnus Spangsberg; Mackey, Abigail L.; Byrjalsen, I.; Bihlet, A.R.

doi:10.1016/j.joca.2021.02.569

Cited by 14 publications

(12 citation statements)

References 45 publications

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“…Accordingly, we found that the circulating levels of irisin were significantly elevated after treadmill exercise, especially with moderate-intensity treadmill exercise. Our results not only established a reliable exercise protocol in rat model for exercise-induced irisin, but also confirmed the results of previous studies showing that moderate treadmill exercise alleviated OA cartilage damage in rat models ( Martins et al, 2019 ; Bjerre-Bastos et al, 2021 ).…”

Section: Discussionsupporting

confidence: 89%

Mechanical Stimulation Protects Against Chondrocyte Pyroptosis Through Irisin-Induced Suppression of PI3K/Akt/NF-κB Signal Pathway in Osteoarthritis

Jia

Yang

Bai

et al. 2022

Front. Cell Dev. Biol.

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Irisin, a myokine secreted by muscle during physical exercise, is known to have biological activities in different cell types. Chondrocyte inflammation and pyroptosis have been shown to play important roles in osteoarthritis (OA). In this study, we investigated the effects of exercise-induced irisin during different intensities of treadmill exercise in a rat OA model and the anti-inflammatory and antipyroptosis mechanism of irisin in OA chondrocytes. Forty-eight SD rats (n = 8) were randomly assigned to control (CG), OA (OAG), OA groups under different intensities of treadmill exercise (OAL, OAM, and OAH), OAM + irisin neutralizing antibodies group (OAM + irisin (NA)). The levels of irisin and the severity of OA between groups were detected using ELISA, histology, immunohistochemistry, X-ray and computed tomography and magnetic resonance imaging. The anti-inflammatory and antipyroptosis mechanisms of irisin were investigated in vitro in OA chondrocytes preincubated with recombinant irisin (0, 5, or 10 ng/ml) for 1 h before treatment with interleukin-1β (IL-1β) for 24 h mRNA and protein expression levels were determined using quantitative reverse transcription polymerase chain reaction, and western blot analyses. Morphological changes and cell death associated with pyroptosis were examined using transmission electron microscopy, flow cytometry and immunofluorescence. Moderate-intensity treadmill exercise increased the levels of irisin, exhibiting the best therapeutic effects on OA which could be suppressed by irisin neutralizing antibodies. Irisin not only recovered the expression of collagen II and attenuated that of MMP-13 and ADAMTS-5 in IL-1β-induced OA chondrocytes by inhibiting the PI3K/Akt/NF-κB signaling pathway, but also inhibited the activity of nod-like receptor protein-3 (NLRP3)/caspase-1, thus ameliorating pyroptosis in chondrocytes. In conclusion, moderate mechanical stimulation protects against chondrocyte pyroptosis through irisin-induced suppression of PI3K/Akt/NF-κB signal pathway in osteoarthritis.

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Section: Discussionsupporting

confidence: 89%

Mechanical Stimulation Protects Against Chondrocyte Pyroptosis Through Irisin-Induced Suppression of PI3K/Akt/NF-κB Signal Pathway in Osteoarthritis

Jia

Yang

Bai

et al. 2022

Front. Cell Dev. Biol.

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“…The data presented in this communication originate from the EFEX-OA-02 exploratory clinical study (Bjerre-Bastos J. J. et al, 2022) in which the acute effect of exercise on biochemical markers reflecting joint tissue turnover in knee OA is investigated. The trial was based on the pilot study, EFEX-OA-01, as previously reported (Bjerre-Bastos et al, 2021a;2021b), and the design is outlined in Figure 1. In EFEX-OA-02, hemoglobin and derived hematocrit were measured to monitor changes as a reflection of rapid fluctuations in PV which could bias the joint biomarker results.…”

Section: Methodsmentioning

confidence: 99%

“…The observed exercise-induced PV changes normalize and stabilize within 30 min after the bout, indicating that PV adjustment may have less relevance outside the acute window of exercise and on the long-term chronic effects of exercise on such markers. Past studies evaluating biochemical markers in an acute exercise setting generally did not adjust for acute plasma volume changes and observed prompt, transient increases in joint biochemical markers could therefore be biased (Andersson et al, 2006;Bjerre-Bastos et al, 2021a;Maren et al, 2022).…”

Section: Perspectivesmentioning

confidence: 99%

An Estimate of Plasma Volume Changes Following Moderate-High Intensity Running and Cycling Exercise and Adrenaline Infusion

et al. 2022

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Introduction: Plasma volume (PV) changes in response to physical activity, possibly as a consequence of adrenergic activation. We estimated changes in PV in response to common exercise modalities; cycling and running as well as adrenaline infusion and control at rest.Methods: On separate days, forty circulatory healthy subjects [aged 60 years (range: 42–75)] with knee osteoarthritis underwent moderate-high intensity cycling, running, and intravenous adrenaline infusion to mimic the circulatory response to exercise. Blood samples were obtained from peripheral veins taken at several pre-defined time points before, during, and after the interventions. PV changes were estimated using venous hemoglobin and the derived hematocrit. The temporal associations between PV and selected biomarkers were explored.Results: Changes in PV were observed during all four interventions, and the response to cycling and running was similar. Compared to rest, PV decreased by -14.3% (95% CI: -10.0 to -18.7) after cycling, -13.9% (95% CI: -10.9 to -17.0) after running, and -7.8% (95% CI: -4.2 to -11.5) after adrenaline infusion.Conclusion: PV decreased in response to moderate-high intensity running and cycling. Adrenaline infusion mimicked the PV change observed during exercise, suggesting a separate influence of autonomic control on blood volume homeostasis. In perspective, a temporal association between PV and biomarker dynamics suggests that consideration of PV changes could be relevant when reporting plasma/serum constituents measured during exercise, but more research is needed to confirm this.

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“…It is worth mentioning markers such as COMP, measuring the turnover of the cartilage oligomeric matrix protein in blood. It seem to be highly elevated after traumatic injury and moderate to high with impact exercise [13,49,50]. CRPM, which measures a metabolite of C-reactive protein, is also elevated in a subset of OA patients and associated with disease progression [51][52][53].…”

Section: On a Side Notementioning

confidence: 99%

Blood and urine biomarkers in osteoarthritis – an update on cartilage associated type II collagen and aggrecan markers

Bay-Jensen

Mobasheri

Thudium

et al. 2021

Current Opinion in Rheumatology

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Purpose of review Osteoarthritis (OA) is a painful disease for which drug development has proven difficult. One major reason for this is the heterogeneity of the disease and the current lack of operationalized means to distinguish various disease endotypes (molecular subtypes). Biomarkers measured in blood or urine, reflecting joint tissue turnover, have been developed and tested during the last decades. In this narrative review, we provide highlights on biomarkers derived from the two most studied and abundant cartilage proteins – type II collagen and aggrecan. Recent findings Multiple biomarkers assessing type II collagen degradation and formation, and aggrecan turnover have been developed. Several markers, such as uCTX-II, have been validated for their association with disease severity and prognosis, as well as pharmacodynamically used to describe the mode of action and efficacy of drugs in development. There is a great need for biomarkers for subdividing patients (i.e., endotyping) and recent scientific advances have not yet come closer to achieving this goal. Summary There is strong support for using biomarkers for understanding OA, reflecting degradation and formation of the joint tissues, focused on type II collagen and aggrecan. There is still a lack of in vitro diagnostics, in all contexts of use.

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Does moderate intensity impact exercise and non-impact exercise induce acute changes in collagen biochemical markers related to osteoarthritis? – An exploratory randomized cross-over trial

Cited by 14 publications

References 45 publications

Mechanical Stimulation Protects Against Chondrocyte Pyroptosis Through Irisin-Induced Suppression of PI3K/Akt/NF-κB Signal Pathway in Osteoarthritis

Mechanical Stimulation Protects Against Chondrocyte Pyroptosis Through Irisin-Induced Suppression of PI3K/Akt/NF-κB Signal Pathway in Osteoarthritis

An Estimate of Plasma Volume Changes Following Moderate-High Intensity Running and Cycling Exercise and Adrenaline Infusion

Blood and urine biomarkers in osteoarthritis – an update on cartilage associated type II collagen and aggrecan markers

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