Abstract
Purpose:Todetermine the suitability of selected blood biomarkers of articular cartilage as mechanosensitive markers and to investigate the dose-response relationship between ambulatory load magnitude andmarkerkinetics 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 eachexperimentalsession, 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 usingcommercialenzyme-linked immunosorbent assays. A two-stage analytical approach was used to determine the suitability of a biomarkerby testing the response to the stress test (criterion I) and thedose-response relationship between ambulatory load magnitude and biomarker kinetics(criterion II). Results.COMP, MMP-3 and IL-6 at all three time pointsafter, MMP-9 at 30 and 60 minutes after, and ADAMTS-4 and CPII atimmediately afterthe stress testshowedan average response to load or an inter-individual variation in response to loadof up to 25% of pre-test levels.Therelation to load magnitude on average or an inter-individual variation in this relationshipwasup to8%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 contextofarticular cartilagemechanosensitivityand its role in joint degeneration and OA.WhileCOMP 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.
Highlights
Physical activity is a prerequisite for maintaining a healthy musculoskeletal system
Answering the central research question of how living articular cartilage responds to joint loads experienced during daily activities represents a major milestone towards understanding articular cartilage health and if a disruption of this response may play a role in the pathomechanics of OA
We investigated at each time point how the response changes with the load by considering the slope of a regression line through the three points defined by the three ambulatory load levels (80% body weight (BW), 100%BW and 120%BW) and the magnitude of the response
Summary
Physical activity is a prerequisite for maintaining a healthy musculoskeletal system. Physical activity in healthy adults reduces the risk of cartilage thinning, cartilage defects, and bone marrow lesions[1] the protective role of joint loading in a physiologic biomechanical and biochemical environment is still controversial[2]. Physical activity can relieve OA symptoms[5], its role in maintaining healthy cartilage and in the initiation and progression of OA in humans remains largely unknown. Answering the central research question of how living articular cartilage responds to joint loads experienced during daily activities represents a major milestone towards understanding articular cartilage health and if a disruption of this response may play a role in the pathomechanics of OA. We are interested in the acute response to 30 minutes of ambulatory load in healthy individuals
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