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

The effect of physical activity on serum cartilage biomarkers is largely unknown. This study is critical to increase our knowledge of the physiological cartilage response to activities of daily living and dynamic tasks by focusing on healthy recreationally active individuals, thus improving our understanding of the complex relationship between cartilage health and the loading that occurs during different types of loading.

Study Overview

• Status: Available
• Conditions: Biochemical Markers
• Intervention / Treatment: Other: Walking; Other: Cycling

Detailed Description

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.

• Study Type: Expanded Access

Contacts and Locations

Study Locations

• Turkey
  • Kocaeli, Turkey
    • Available
    • Kocaeli University Faculty of Medicine Hospital
  • Sakarya, Turkey
    • Available
    • Sakarya University Applied Sciences Physiotherapy and Rehabilitation Application and Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Study Population

Volunteers will be instructed to minimize all sports activities 48 hours before the experimental days, but normal daily activities such as walking and climbing stairs will be allowed. Volunteers will also be advised to maintain the same daily routine and eat the same foods on the evaluation days.

Description

Inclusion Criteria:

• Healthy male volunteers between the ages of 20-35
• Those who do physical activity for at least 30 minutes two to three days a week
• 17 healthy male individuals without any health problems will be included.

Exclusion Criteria:

• Those with acute or chronic injuries in their lower extremities
• Those with musculoskeletal disorders in their lower extremities
• Those who have undergone hip and/or knee surgery
• Those with cardio-pulmonary problems that prevent them from exercising

Study Plan

How is the study designed?

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Walking group; Healthy male volunteers aged 20-35 Engaged in physical activity for at least 30 minutes, two to three days a week Individuals without any health issues	Other: Walking; Participants will perform 30 minutes of walking and cycling exercises. During the cycling and walking exercises, heart rate will be calculated using the Karvonen formula based on heart rate reserve. HRmax (maximum heart rate)=220-age HRR (%)(heart rate reserve)= (HR-HRrest)/(HRmax-HRrest)*100 Blood samples will be collected from participants before starting the exercise, at the end of the 30-minute exercise session, and twice more at 30-minute intervals. The same participants will perform the cycling exercise half an hour later, and the same procedures will be applied.; Other: Cycling; Cycling
Cycling group; Healthy male volunteers aged 20-35 Engaged in physical activity for at least 30 minutes, two to three days a week Individuals without any health issues	Other: Walking; Participants will perform 30 minutes of walking and cycling exercises. During the cycling and walking exercises, heart rate will be calculated using the Karvonen formula based on heart rate reserve. HRmax (maximum heart rate)=220-age HRR (%)(heart rate reserve)= (HR-HRrest)/(HRmax-HRrest)*100 Blood samples will be collected from participants before starting the exercise, at the end of the 30-minute exercise session, and twice more at 30-minute intervals. The same participants will perform the cycling exercise half an hour later, and the same procedures will be applied.; Other: Cycling; Cycling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serum cartilage biomarkers	cartilage oligomeric matrix protein (COMP) Matriks metaloproteinaz YKL-40 Rezistin	From enrollment to the end of treatment at 1 week

Collaborators and Investigators

• Sponsor: Kocaeli University
• Collaborators: Sakarya University of Applied Sciences

Study record dates

Study Major Dates

• Study Start: January 1, 2025
• Primary Completion: February 28, 2025
• Study Completion: March 1, 2025

Study Registration Dates

• First Submitted: December 27, 2024
• First Submitted That Met QC Criteria: January 2, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 2, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: serum cartilage; Osteoblastic activity; Osteoclastic activity
• Other Study ID Numbers: Sakarya University of Applied

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No