Evaluation of Different Serum Cartilage Biomarkers in the Acute Response to Walking and Cycling in Healthy Male Subjects

Biomarkers can be used to monitor cartilage metabolism and serve as prognostic or diagnostic markers to detect changes in joint structure (8). Most of these biomarkers are essential components of the cartilage extracellular matrix (ECM). The measurement of cartilage biomarkers is based on the principle that osmotic and mechanical loading triggers the efflux of proteolytically produced ECM fragments into the synovial fluid and then out of the joint capsule. Thus, biomarker concentrations can be measured by immunoassays in synovial fluid, blood, and urine. Similarly, biomarker concentrations have been used to investigate the acute or long-term effects of exercise on articular cartilage health and metabolism.

The most studied serum cartilage biomarker is cartilage oligomeric matrix protein (COMP). COMP, also known as thrombospondin-5, is a pentameric glycoprotein composed of five identical subunits. The C-terminal end of each monomer interacts with numerous KDHM proteins, such as collagen II, collagen IX, matrilins, and proteoglycans (9). In addition, COMP affects collagen secretion and fibrillogenesis, thereby influencing the rate of fibril formation, organization, and diameter (10). Due to these interactions with other KDHM proteins, COMP has an important role in the assembly and structure of the cartilage matrix, determining its mechanical properties.

Based on these properties, COMP has been widely studied in terms of acute loading and has been shown to be mechanosensitive (11). Serum COMP levels have been found to vary between -16% and +39% after 30 min of moderate running interventions (12). However, no increase in serum concentration was detected in response to other acute exercises, such as knee flexion or repeated lumbar flexion/extension (13). This suggests that the acute serum COMP response is dependent on joint loading characteristics.

Other biomarkers of interest are proteolytic enzymes involved in the degradation of cartilage KDHM components. Matrix metalloproteinases (MMPs) are a family of enzymes that vary in substrate specificity and primary structure.

Some MMP family members play a role in both KDHM remodeling and pathological degradation. For example, MMP-3 (stromelysin) degrades most components of KDHM and activates other MMPs such as MMP-9 (gelatinase B), which itself plays an important role in the development of OA (14).

YKL-40 is another KDHM protein involved in cartilage pathogenesis. Although the function of YKL-40 has not been defined in detail, it has been shown to be involved in general tissue remodeling and inflammatory processes as a glycosylase (15). YKL-40 levels increase during joint inflammation, and resistin levels are also elevated by inflammatory stimuli. Resistin is an adipokine that was initially associated with obesity and insulin resistance in rodents.

The response of MMPs, YKL-40, and resistin concentrations to exercise has been previously investigated. Marathon running has been shown to increase serum MMP-3 (+142%), YKL-40 (+56%), and resistin (+107%) concentrations immediately after the marathon compared to baseline values (16).

Type II collagen is a major component of articular cartilage. The degradation of type II collagen occurs via the activity of collagenases and MMP-9. Coll2-1 is a specific peptide epitope located on the triple helix of type II collagen molecules and is a marker of cartilage degeneration.

The nitrated form of Coll2-1 is called Coll2-1 NO2 and reflects oxidative-related cartilage matrix degradation. Serum concentrations of Coll2-1 (-13%) and Coll2-1 NO2 (-19%) have been shown to decrease after a marathon run (17).

Nagaoka et al. (18) evaluated the cartilage collagen metabolism of athletes exposed to intense joint loading. They measured both type II collagen synthesis and degradation biomarkers in urine. The results showed that type II collagen degradation increased in response to endurance exercises that included intense joint loading, especially in athletes who performed frequent jumping movements such as volleyball, basketball and handball.

The aim of our study was to examine the acute effect of two commonly used exercise interventions (walking and cycling) on the correlation of serum biomarkers reflecting cartilage extracellular matrix metabolism, COMP, YKL-40, and MMP3.