Experimental-analytical approach to assessing mechanosensitive cartilage blood marker kinetics in healthy adults: Dose-response relationship and interrelationship of nine candidate markers

Mündermann A, Herger S, Vach W, Liphardt AM, Nüesch C, Egloff C (2022)


Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 10

Article Number: 490

DOI: 10.12688/f1000research.52159.2

Abstract

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.

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APA:

Mündermann, A., Herger, S., Vach, W., Liphardt, A.-M., Nüesch, C., & Egloff, C. (2022). Experimental-analytical approach to assessing mechanosensitive cartilage blood marker kinetics in healthy adults: Dose-response relationship and interrelationship of nine candidate markers. F1000Research, 10. https://doi.org/10.12688/f1000research.52159.2

MLA:

Mündermann, Annegret, et al. "Experimental-analytical approach to assessing mechanosensitive cartilage blood marker kinetics in healthy adults: Dose-response relationship and interrelationship of nine candidate markers." F1000Research 10 (2022).

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