Dose-Response Relationship of Ambulatory Load and Cartilage - Pilot Study

The current state of research in the field and of our own research clearly shows that the in vivo mechanobiology of articular cartilage is poorly understood. Previous results of changes in cartilage biomarker concentrations after ambulatory exercise raise the following question:

Do load-induced changes in blood biomarkers for articular cartilage (COMP) depend on the physiological load magnitude? To generate initial data for answering this question, we will establish the experimental framework to systematically study the in vivo mechanobiology of human articular cartilage to address the following aims.

• To obtain pilot data for investigating the in vivo dose-response relationship of weight-bearing and blood levels of mechanosensitive biomarker of articular cartilage using controlled load- bearing as experimental paradigm.
• To provide pilot data for comparing ambulatory biomechanics between the controlled load- bearing conditions.

The experimental setting consists of a 30-minutes walking stress test under three loading conditions: A: 80 %, B: 100% and C: 120% bodyweight. Unloading will be achieved through an unloading system and additional loading with an adjustable weight vest. Before and after the walking stress test, venous blood samples will be taken at five time points. The biomarker concentration is measured with a commercial available enzyme-linked immunosorbent assay (ELISA).

Hypothesis Our working hypothesis is that there is a dose-response relationship between the temporarily increased or decreased load and the load-induced change in COMP level in the blood serum. We assume that serum COMP concentration increases with increasing accumulated load on the knee cartilage simulated through the three different loading conditions.