The aim of EFEX-OA-02 is to explore how running, cycling, exercise simulation and resting acutely influence collagen and proteoglycan homeostasis in OA, as reflected by changes in collagen and proteoglycan levels in urine and serum.

Inclusion Criteria:

1. Cumulated Osteoarthritis Kellgren-Lawrence radiological grade of at least 2 in the tibio-femoral joints diagnosed by screening X-ray.
2. 40 to < 75 years of age at time of signing the informed consent.
3. Body weight > 50 and < 100 kg and BMI in the range 18.5-35 kg/m2 .
4. Male or female.
5. Able to attend all four study sessions and comply with the dietary and activity restrictions.
6. Able to provide informed consent

Exclusion Criteria:

Medical conditions:

1. Osteoarthritis Kellgren-Lawrence radiological grade of 4 in one or both knees.
2. Cumulated osteoarthritis Kellgren-Lawrence radiological grade no higher than 1.
3. History of arthroscopy or intra-articular administration of corticosteroids or hyaluronic acid into the target knee within 6 months before screening.
4. Previous arthroplasty of knee or hip.
5. Intention to have major surgery during the timeframe of the study.
6. Secondary OA related to e.g. any known trauma including cruciate ligament tears, meniscus tears and cartilage damage, dysplasia, aseptic osteonecrosis, acromegaly, Paget disease, Stickler syndrome, hemochromatosis, gout, chondrocalcinosis (pseudogout).
7. Current treatment with beta-receptor adrenergic antagonists (beta-blockers), MAO inhibitor, systemic corticosteroid treatment in doses equivalent to > 10 mg prednisolone per day, or vitamin K antagonists, new oral anticoagulants, fractionated and non-fractionated heparin.
8. Active systemic infection.
9. Active systemic inflammatory or autoimmune disease.
10. Any sign of previous or current cardiovascular disease.
11. Not currently an active athlete or highly trained individual.

Other exclusion criteria:

1. Legal incapacity or limited legal capacity.
2. Inability to communicate or cooperate with the investigator or to comply with the requirements of the entire study.
3. Categorized as being very difficult to draw blood from, as evaluated by the investigator.
4. Current alcohol abuse and/or inability to refrain from intake of alcoholic beverages for 24 hours prior to the study intervention.
5. Other factors, e.g. self-reported drug abuse, which in the opinion of the investigator may interfere with the performance of the study.
6. Site staff, study staff members and study staff family members.
7. Other concomitant disease compromising or otherwise significantly affecting ECM turnover in the opinion of the investigator.