Evaluation of serum ARGS neoepitope as an osteoarthritis biomarker using a standardized model for exercise-induced cartilage extra cellular matrix turnover

Bjerre-Bastos, J.J.; Nielsen, Henning Bay; Andersen, J.R.; He, Yi; Karsdal, Morten; Bay‐Jensen, Anne‐Christine; Boesen, Mikael; Mackey, Abigail L.; Bihlet, A.R.

doi:10.1016/j.ocarto.2020.100060

Cited by 9 publications

(10 citation statements)

References 40 publications

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“…44 ARGS-aggrecan and PA has also been evaluated in a OA-population. 45 That study showed that serum ARGS-aggrecan has a low sensitivity to PA which is in line with the results in this study, but the measurements were only collected for 24 hours.…”

Section: Discussionsupporting

confidence: 90%

Associations Between Physical Activity, Self-reported Joint Function, and Molecular Biomarkers in Working Age Individuals With Hip and/or Knee Osteoarthritis

Östlind

Eek

Stigmar

et al. 2022

Clin Med�Insights�Arthritis�Musculoskelet Disord

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Objective: Previous research has suggested an association between physical activity (PA), joint function, and molecular biomarkers, but more studies are needed. The aim of this study was to explore the associations between PA or self-reported joint function and molecular biomarkers of cartilage and inflammation in individuals with hip and/or knee osteoarthritis (OA). Specific objectives were to explore the correlations between (1) the change over 3 months in self-reported PA/joint function and the change in molecular biomarkers (2) objectively measured PA and molecular biomarkers measured at 3-month follow-up. Design: Working age participants (n = 91) were recruited from a cluster randomized controlled trial. Self-reported PA, joint function, and serum samples were collected at baseline and after 3 months. Serum concentrations of the inflammatory marker C-reactive protein (CRP) and the cartilage markers Alanine-Arginine-Glycine-Serine (ARGS)-aggrecan, cartilage oligomeric matrix protein (COMP), and type II collagen C2C were analyzed by immunoassays. Objectively measured PA (steps/day) was collected during 12 weeks from activity trackers used by 53 participants. Associations were analyzed with Spearman’s rank correlation. Results: There was a weak negative correlation between the change in self-reported PA and the change in COMP ( rs = −0.256, P = .040) but not for the other molecular biomarkers. There were no correlations between the change in self-reported joint function and the change in molecular biomarkers or between the average steps/day and the molecular biomarkers at follow-up ( rs ⩽ −0.206, P ⩾ .06). Conclusion: In general, no or only weak associations were found between PA/joint function and molecular biomarkers. Future research recommends including participants with lower PA, extend the follow-up, and use a design that allows comparisons.

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Section: Discussionsupporting

confidence: 90%

Associations Between Physical Activity, Self-reported Joint Function, and Molecular Biomarkers in Working Age Individuals With Hip and/or Knee Osteoarthritis

Östlind

Eek

Stigmar

et al. 2022

Clin Med�Insights�Arthritis�Musculoskelet Disord

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“…Past studies found that walking exercise 16,17 and combined endurance and strength training 18 significantly increased serum levels of COMP. In a study by our group serum levels of aggrecan fragment ARGS neoepitope increased significantly following moderate intensity cycling and running 15 . In another study, Helmark et al compared a leg-press exercise group with a non-exercise group and found increased urine levels of aggrecan in the exercise group, no difference in Fig.…”

Section: Discussionmentioning

confidence: 70%

“…The study was approved by the Danish national ethics committee (approval number: H-18038807) and followed the procedural and ethical standards according to the Helsinki Declaration. Additional details are described elsewhere 15 .…”

Section: Permissionsmentioning

confidence: 99%

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

Nielsen

Andersen

et al. 2021

Osteoarthritis and Cartilage

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“…The pathological relevance of serum ARGS in OA is still under investigation. Recent data found a negative correlation between ARGS and radiographic severity in patients with OA ( 20 ), suggesting that, in patients with OA not treated with ADAMTS‐5 inhibitors, the ARGS levels in serum may be reflective of the volume of remaining cartilage. Another report investigating associations between synovial fluid ARGS levels and risk of radiographic progression of OA in individuals who had previously undergone meniscectomy found a weak negative association between synovial fluid ARGS and risk of progression ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Safety, Tolerability, and Pharmacodynamics of the ADAMTS‐5 Nanobody M6495: Two Phase 1, Single‐Center, Double‐Blind, Randomized, Placebo‐Controlled Studies in Healthy Subjects and Patients With Osteoarthritis

Bihlet,

Balchen,

Goteti

et al. 2024

ACR Open Rheumatology

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ObjectiveTo assess the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple injections of M6495, a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS‐5) nanobody, in healthy volunteers and patients with osteoarthritis.MethodsTwo randomized, placebo‐controlled, double‐blind studies were performed. Study 1 enrolled 54 healthy male volunteers who received one subcutaneous (s.c.) injection of M6495 (1‐300 mg) or placebo (ratio 2:1), evaluating safety, PK, and PD as changes in the serum aggrecan fragment alanine‐arginine‐glycine‐serine (ARGS). Study 2 enrolled 32 patients with osteoarthritis with Kellgren–Lawrence grades 2 to 4 and pain greater than or equal to 40 on the Western Ontario and McMaster Universities Arthritis Index pain subscale at screening and evaluated the safety, PK, and PD of three doses every two weeks (75‐300 mg per dose) or six once‐weekly M6495 s.c. doses (300 mg) or placebo (ratio 3:1) over 106 days’ follow‐up.ResultsM6495 in single and multiple doses of less than or equal to 300 mg s.c. weekly was well tolerated with no clinically significant changes in any safety parameter. Adverse events more frequently reported in the M6495 groups were mostly mild cases of injection site reactions, myalgia, and nausea, which resolved after treatment cessation. The elimination half‐life of single s.c. doses of M6495 ranged from 79 to 267 hours. M6495 administration substantially reduced serum ARGS levels, indicative of target engagement and indicating disease‐modifying potential of M6495.ConclusionTreatment with M6495 in single and multiple doses up to and including 300 mg s.c. was found to be well tolerated and adequately safe for further clinical evaluation of potential disease‐modifying effects.

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Evaluation of serum ARGS neoepitope as an osteoarthritis biomarker using a standardized model for exercise-induced cartilage extra cellular matrix turnover

Cited by 9 publications

References 40 publications

Associations Between Physical Activity, Self-reported Joint Function, and Molecular Biomarkers in Working Age Individuals With Hip and/or Knee Osteoarthritis

Associations Between Physical Activity, Self-reported Joint Function, and Molecular Biomarkers in Working Age Individuals With Hip and/or Knee Osteoarthritis

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

Safety, Tolerability, and Pharmacodynamics of the ADAMTS‐5 Nanobody M6495: Two Phase 1, Single‐Center, Double‐Blind, Randomized, Placebo‐Controlled Studies in Healthy Subjects and Patients With Osteoarthritis

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