Exercise-induced Irisin in Individuals With Knee Osteoarthritis.

The most commonly used measurement tool to assess pain is the Visual Analog Scale (VAS). Patients are asked to rate the intensity of their pain at rest and during activity. A score of 0 indicates no pain, while a score of 10 indicates unbearable pain.

To measure the range of motion of knee flexion and extension, the pivot point of the goniometer is the lateral condyle of the femur while the patient is in the prone position. One of the arms of the goniometer is fixed parallel to the lateral midline of the femur. The movable arm follows the fibula. The degree that the patient can perform is recorded.

Quadriceps muscle strength will be assessed with a hand-held dynamometer (Lafayette). The participant is in a sitting position with hips and knees flexed to 90°. The dynamometer is placed on the anterior surface of the leg just proximal to the ankle. During the measurement, the participant is asked to apply maximum pushing force against the device for 5 seconds. The measured force will be recorded in 'kg'.

The six-minute walk test (6MWT) will be used to determine the functional level. The 6MWT is used to evaluate the person's endurance and ability to walk long distances. The person walks the maximum distance they can walk as fast as possible on a 30-meter flat track in 6 minutes. The distance the person walked is added up at the end of the test and the longer distance indicates better performance.

KOOS is a self-report scale used to assess symptoms and functional status that may develop due to knee injuries and osteoarthritis. The scale, which questions the last week, has 5 subgroups: symptoms, pain, functional status related to daily living activities, functional status in sports and leisure activities, and quality of life related to the knee, and the scale consists of a total of 42 questions. Each subsection is scored between 0 and 100 points, with 0 points indicating a serious problem and 100 points indicating no problem.

The Knee and Hip Osteoarthritis Quality of Life Scale (OAKHQOL) will be used to assess quality of life. The Knee and Hip Osteoarthritis Quality of Life Scale consists of 5 subsections: physical activity, mental health, pain, social functions and social support. The scale consists of 43 items. Each item in the scale is scored between 0 and 10, taking into account the last 4 weeks. 0 means 'not at all', 10 means 'very extreme, constant'. The calculation is made out of 100 according to the average score of the items in each subsection. As the total score increases, the quality of life increases.

The presence of depression will be assessed with the Beck Depression Index-II (BDI-II). The BDI-II consists of 21 items. Participants are asked to give a score between 0 and 3 for each item, taking into account the last week. The severity of depression increases as the total score obtained from the scale increases. The main difference between the BDI-II and previous versions is that it includes items that aim to measure structures such as loss of energy, worthlessness, appetite disorders and concentration.

The Fatigue Severity Scale will be used to assess fatigue. The Fatigue Severity Scale assesses fatigue in the last month. The scale consists of 9 items and the items are scored between 0 and 7. A score of 0 means I completely disagree, a score of 7 means I agree. The scale score is obtained by dividing the total score by the number of items. The higher the score, the higher the fatigue level.

The Pittsburgh Sleep Quality Index (PSQI) will be used to assess sleep quality. The scale, which assesses the person's sleep quality in the last month, begins with 4 open-ended questions and consists of a total of 24 questions. In the PSQI assessment, 18 questions answered by the person themselves are used in scoring. The PSQI has 7 components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, sleeping pill use, and daytime dysfunction. Each question is answered on a scale of 0-3. The sum of the 7 component scores constitutes the total PSQI score. The total score of the scale is between 0 and 21 points. A total score of 5 or less indicates good sleep quality, while a score above 5 indicates poor sleep quality.

Blood samples will be collected from the participants at the beginning of the study and after 8 weeks of exercise (1 day after the last exercise). Blood samples will be centrifuged at 3000 rpm at +4 0C for 10 minutes to separate plasma and samples will be collected in aliquots in Eppendorf tubes and stored at -80 0C until the day of the study. Serum irisin level will be determined using the human irisin Enzyme-Linked Immunosorbent Assay (ELISA) test kit.

Weight and height will be combined to report BMI in kg/m^2

Multivariate analyses will be carried out with control variables;

• Body mass index (Weight and height will be combined to report BMI in kg/m^2)
• Pain VAS score
• Quadriceps strength assessed with hand-held dynamometer (HHD) (Kg)
• Six-minute walk test (m)
• Knee Injury and Osteoarthritis Outcome Score
• The Knee and Hip Osteoarthritis Quality of Life Scale (OAKHQOL) Score
• Beck Depression Index-II (BDI-II) Score
• Fatigue Severity Scale Score
• Pittsburgh Sleep Quality Index (PSQI) Score
• Range of motion (degrees)