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).