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Experimental-analytical approach to assessing mechanosensitive cartilage blood marker kinetics in healthy adults: dose-response relationship and interrelationship of nine candidate markers [version 1; peer review: 1 approved, 1 approved with reservations]

Herger, Simon ; Vach, Werner ; Liphardt, Anna-Maria ; Nüesch, Corina ; Egloff, Christian ; Mündermann, Annegret

F1000 research, 2021, Vol.10, p.490 [Periódico revisado por pares]

England: F1000 Research Ltd

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  • Título:
    Experimental-analytical approach to assessing mechanosensitive cartilage blood marker kinetics in healthy adults: dose-response relationship and interrelationship of nine candidate markers [version 1; peer review: 1 approved, 1 approved with reservations]
  • Autor: Herger, Simon ; Vach, Werner ; Liphardt, Anna-Maria ; Nüesch, Corina ; Egloff, Christian ; Mündermann, Annegret
  • Assuntos: Adult ; Biomarkers ; cartilage biomarkers ; cartilage mechanosensitivity ; Cartilage Oligomeric Matrix Protein ; Cartilage, Articular ; dose-response relationship ; eng ; Humans ; Interleukin-6 ; Kinetics ; Matrix Metalloproteinase 3 ; Matrix Metalloproteinase 9 ; mechanical loading ; walking stress test
  • É parte de: F1000 research, 2021, Vol.10, p.490
  • Descrição: Purpose: To determine the suitability of selected blood biomarkers of articular cartilage as mechanosensitive markers and to investigate the dose-response relationship between ambulatory load magnitude and marker kinetics in response to load.  Methods: Serum samples were collected from 24 healthy volunteers before and at three time points after a 30-minute walking stress test performed on three test days. In each experimental session, one of three ambulatory loads was applied: 100% body weight (BW); 80%BW; 120%BW. Serum concentrations of COMP, MMP-3, MMP-9, ADAMTS-4, PRG-4, CPII, C2C and IL-6 were assessed using commercial enzyme-linked immunosorbent assays. A two-stage analytical approach was used to determine the suitability of a biomarker by testing the response to the stress test (criterion I) and the dose-response relationship between ambulatory load magnitude and biomarker kinetics (criterion II).  Results. COMP, MMP-3 and IL-6 at all three time points after, MMP-9 at 30 and 60 minutes after, and ADAMTS-4 and CPII at immediately after the stress test showed an average response to load or an inter-individual variation in response to load of up to 25% of pre-test levels. The relation to load magnitude on average or an inter-individual variation in this relationship was up to 8% from load level to load level. There was a positive correlation for the slopes of the change-load relationship between COMP and MMP-3, and a negative correlation for the slopes between COMP, MMP-3 and IL-6 with MMP-9, and COMP with IL6.  Conclusions: COMP, MMP-3, IL-6, MMP-9, and ADAMTS-4 warrant further investigation in the context of articular cartilage mechanosensitivity and its role in joint degeneration and OA. While COMP seems to be able to reflect a rapid response, MMP-3 seems to reflect a slightly longer lasting, but probably also more distinct response. MMP-3 showed also the strongest association with the magnitude of load.
  • Editor: England: F1000 Research Ltd
  • Idioma: Inglês

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