The aim of this study was to elucidate whether the levels of serum biomarkers reflect the progression of osteoarthritis (OA) induced by different levels of exercise. Thirty-five Wistar rats subjected to anterior cruciate ligament transaction (ACLT) were divided into three groups: Control, moderate running, and intense running. Twelve rats (moderate running without ACLT) were allocated as a naive group. Running was performed on a motorized treadmill, at a speed of 18 m/min for 30 min/day (moderate and naive) or 60 min/day (intense) for 3 days per week. After 2 or 4 weeks, OA histopathology in the knees was evaluated using the Osteoarthritis Research Society International (OARSI) score, and the serum levels of cleaved collagen type II (C2C) and procollagen II C-propeptide (CPII) were analyzed. The OARSI score deteriorated in the intense running group after 2 weeks and the serum C2C/CPII ratio suggested the development of OA. At 4 weeks, the C2C/CPII ratio suggested there would be deterioration in the OARSI score but the score did not differ significantly between the moderate and intense running groups. C2C/CPII ratio had 13-25% correlation with the OARSI histological score. Thus, in rat experimental OA, the OARSI score could be partially predicted by the C2C/CPII ratio as a serum biomarker of OA. Keywords: cartilage metabolism; osteoarthritis; running exercise; rats; biomarker Osteoarthritis (OA) of the knee, a common joint disorder among elderly people, is caused by aging, overuse, trauma, and other complicating factors, and leads to degenerative structural changes. In daily life, exercise is encouraged for individuals with poor locomotion caused by OA, but excessive stress can induce cartilage degeneration.1,2 The anterior cruciate ligament contributes to dynamic stability of the knee joint, and injury to this structure is a crucial factor leading to OA of the knee in human subjects, 3 rats, 4 and many other species. 5,6 Clinically, OA of the knee is treated using physical therapies such as stretching, muscle training, gait control, and some pharmacotherapeutic methods. 7,8 Moderate mechanical loading maintains the integrity of articular cartilage, but both disuse and overuse can result in cartilage degradation.9-13 Forced mobilization accelerated OA damage in rats subjected to anterior cruciate ligament transaction (ACLT). 9 In another report, rats made to exercise following ACLT developed more cartilaginous lesions than did controls with no exercise, but the lesions in the control rats were usually as severe as those in the exercising rats. 4 From a structural standpoint, articular cartilage is composed of chondrocytes and an extracellular matrix rich in molecules such as type II collagen and aggrecan. In individuals with OA, these components are degraded by various enzymes such as a disintegrin metalloproteinase with thrombospondin motifs (ADAMTS) and matrix metalloproteinases (MMPs).5,14-16 Cartilage degradation can be attributed to an imbalance between the anabolic and catabolic activities of chon...