Excess of eccentric exercise, mechanical load on the knee joint and osteoarthritis in C57BL/6 mice

Abstract

Osteoarthritis (OA) is a degenerative chronic disease that induces cartilage degradation and is very common in the knee joint. OA progression occurs due to excess load in the joint as well as systemic or local inflammation. Physical exercise is a commonly used therapy to prevent and treat this illness, attenuating the symptoms, however studies that exhibit controversial results still exist, which could be explained by the volume, intensity, and type of exercise used. Scientific investigations demonstrate that excessive exercise may cause an onset of osteoarthritis, which can be explained through joint overload, and/or increasing enzymes related to cartilage degradation. Furthermore our study group has verified that mice submitted to downhill excessive training presented low grade systemic inflammation, evidenced by an increase in pro-inflammatory cytokines. The hypothesis to explain the high level of inflammation in this type of exercise is mechanical, histological, and biochemical alterations in muscles, such as the increase in serial sarcomeres and a shift in the length-tension relationship. Therefore, the aim of the present study is to verify the differences in osteoarthritis progression, muscular inflammation, and shift in sarcomere structure among C57BL/6 mice moderately trained in downhill and uphill, and excessively trained in downhill and uphill. The mice will be divided into 5 groups: sedentary (S; sedentary mice); trained downhill (TRD; mice submitted to downhill training protocol); trained uphill (TRU; mice submitted to uphill training protocol); downhill excessive training (DET; mice submitted to downhill overtraining protocol); uphill excessive training (UET; mice submitted to uphill overtraining protocol). The content and activation protein related to OA and inflammation will be evaluated in the medial vastus and knee joint through the immunoblotting technique, and OA progression and sarcomere structure will be evaluated using established histological technique and a validated histological scoring protocol. The comparison between groups will be performed using variance analysis followed by a multiple comparison of means test. A significance level of pd0.05 will be adopted. (AU)