Knee osteoarthritis is a common degenerative joint disease characterized by pain, stiffness, and functional limitation, significantly affecting quality of life. In addition to mechanical factors, cartilage degradation and extracellular matrix remodeling play a key role in disease progression. Therefore, identifying reliable biomarkers reflecting disease severity has become an important research focus.

Cartilage oligomeric matrix protein (COMP) is a structural component of cartilage associated with cartilage turnover, while matrix metalloproteinase-3 (MMP-3) is a proteolytic enzyme involved in extracellular matrix degradation. Both biomarkers have been suggested to be elevated in osteoarthritis and may reflect disease severity.

The aim of this cross-sectional observational study is to evaluate the relationship between serum COMP and MMP-3 levels and clinical and radiological severity in patients with knee osteoarthritis. Pain severity will be assessed using the Visual Analog Scale (VAS), functional status with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and radiological severity with the Kellgren-Lawrence classification. Functional performance will also be evaluated using the 5 Times Sit-to-Stand Test.

Additionally, serum COMP and MMP-3 levels will be compared between patients with knee osteoarthritis and healthy controls. The findings of this study are expected to contribute to a better understanding of the relationship between biochemical markers and clinical severity in osteoarthritis and may provide insight into their potential diagnostic and prognostic value.

Knee osteoarthritis (OA) is one of the most prevalent musculoskeletal disorders and a leading cause of pain, disability, and reduced quality of life worldwide. The pathophysiology of OA involves not only mechanical degeneration but also complex biological processes including cartilage degradation, synovial inflammation, and extracellular matrix remodeling. In recent years, there has been growing interest in identifying biochemical markers that can reflect disease severity and progression.

Cartilage oligomeric matrix protein (COMP) is a non-collagenous extracellular matrix protein predominantly found in cartilage, and its serum levels are considered to reflect cartilage turnover and degradation. Matrix metalloproteinase-3 (MMP-3) is an important proteolytic enzyme involved in the breakdown of extracellular matrix components and plays a key role in cartilage destruction in osteoarthritis. Elevated levels of these biomarkers have been reported in patients with OA and may be associated with disease severity.

This cross-sectional observational study is designed to investigate the relationship between serum COMP and MMP-3 levels and clinical and radiological severity in patients with knee osteoarthritis. A total of 60 participants will be included, consisting of 30 patients diagnosed with knee osteoarthritis and 30 healthy controls with similar demographic characteristics.

Clinical assessment will include pain severity measured by the Visual Analog Scale (VAS) and functional status assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Functional performance will be evaluated using the 5 Times Sit-to-Stand Test. Radiological severity will be determined according to the Kellgren-Lawrence classification based on standard knee radiographs.

Venous blood samples will be collected under aseptic conditions. Serum samples will be separated by centrifugation and stored under appropriate conditions until analysis. Serum COMP and MMP-3 levels will be measured using validated enzyme-linked immunosorbent assay (ELISA) kits in an accredited laboratory. All samples will be analyzed according to the manufacturer's instructions.

The primary objective of the study is to evaluate the association between serum COMP and MMP-3 levels and clinical and radiological severity parameters in knee osteoarthritis. Secondary objectives include comparing biomarker levels between patients and healthy controls and exploring the independent predictive value of these biomarkers after adjusting for potential confounding factors such as age, sex, and body mass index.

It is hypothesized that serum COMP and MMP-3 levels will be significantly higher in patients with knee osteoarthritis compared to healthy controls and will show a positive correlation with pain severity, functional impairment, and radiological grade. The findings of this study may contribute to a better understanding of the role of biochemical markers in osteoarthritis and support their potential use in clinical assessment and disease monitoring.

Inclusion Criteria:

• Age between 40 and 75 years Male and female participants For patient group: clinically and radiologically confirmed diagnosis of knee osteoarthritis Kellgren-Lawrence grade 2-3 (or 2-4 if you decide to include advanced stages) Ability to understand and comply with study procedures Willingness to participate and provision of written informed consent For control group: absence of knee pain and no radiographic evidence of knee osteoarthritis

Exclusion Criteria:

• Presence of inflammatory rheumatic diseases (e.g., rheumatoid arthritis, ankylosing spondylitis) History of acute knee trauma Previous knee surgery (e.g., arthroplasty or arthroscopy) History of septic arthritis or active infection History of malignancy Severe systemic diseases (e.g., advanced cardiac, renal, or hepatic failure) Neuromuscular disorders affecting lower extremity function Intra-articular injection (e.g., corticosteroids, PRP) within the last 3 months Other conditions that may cause knee pain apart from osteoarthritis Cognitive or psychiatric conditions preventing compliance with study procedures Refusal to provide informed consent

The study population will consist of adult participants aged 40-75 years recruited from the outpatient clinic of Physical Medicine and Rehabilitation. The patient group will include individuals with clinically and radiologically confirmed knee osteoarthritis, while the control group will consist of age- and sex-matched healthy volunteers without knee pain or radiographic evidence of osteoarthritis. All participants will be able to comply with study procedures and will provide written informed consent prior to enrollment.