Razi Journal of Medical Sciences

Mendeley  

Zotero  

Rasouli S H, Farzanegi P, Abbaszadeh H. The effect of aerobic training and hyaluronic acid on expression of MYOD and MURF-1 genes in experimental arthritis model rats. RJMS 2021; 28 (3) :48-58
URL: http://rjms.iums.ac.ir/article-1-6354-en.html

 Background & Aims: Osteoarthritis is the most common joint disease and its main pathological manifestation at the tissue level is local destruction of articular cartilage, which manifests itself in mobile joints by destruction of articular cartilage with new ossification at the surface and periphery of the affected joints (1). Research shows that several factors are involved in the formation of osteoarthritis. These include biochemical or systemic factors (such as genetics, aging, food intake, estrogen intake, bone density, and metabolic syndrome) and biomechanical factors such as muscle weakness, joint stiffness, and joint damage (2). Cell studies report that growth and regeneration of damaged muscle is done by satellite cells (5). Regarding the activation of satellite cells from the off state, studies show multiaxial processes in this field (7). Activation of The Myogenic Regulatory Factors (MRFs) and a group of chain transcription factors including MURF-1 and myoD lead to the participation of these factors in the stages of myogenic development (5). Most studies on osteoarthritis of the knee joint have focused on the tissue of the knee joint, and the effect of non-surgical methods including hyaluronic acid injection and even exercise in osteoporosis of the knee on satellite cell activity or activation of MRFs and factors of chain transcription loop including myoD, the skeletal muscle involved in the knee joint of patients have not been studied or are difficult to access. The present study sought to answer the question whether hyaluronic acid injection and exercise affect the expression of MURF-1 and myoD genes in the gastrocnemius muscle of experimental osteoarthritis rats.
Methods: In this experimental study, 35 adult 8-week-old male Wistar rats were divided into 5 groups, which included: 1) control-healthy, 2) control-patient, 3) patient + exercise, 4) patient + hyaluronic acid, 5) patient + exercise + hyaluronic acid. Knee osteoarthritis was surgically treated in rats. In the hyaluronic acid group, they received a concentration of 30 micrograms once a week for three weeks. Rats in the exercise group exercised on animal treadmills five times a week at a speed of 16 to 18 m/min. 48 hours after the end of the protocol, gastrocnemius muscle tissues were isolated and the expression of MYOD and MURF-1 genes were measured by Real-Time PCR (RT-PCR).
Results: According to the calculated F value (5.4) and its significance at the level of P = 0.001, there is a significant difference between different groups. Figure 1 shows the expression of MURF-1 gene, a significant decrease in the healthy, exercise, hyaluronic acid, hyaluronic acid + exercise groups, compared with the patient group (p = 0.001). Hyaluronic acid + exercise group had a significant decrease compared to hyaluronic acid and exercise groups (p = 0.001). The expression values of MYOD gene according to the calculated F-value (26.47) and its significance at P = 0.001 level indicate the existence of significant differences between different research groups. Accordingly, in comparison with the patient and hyaluronic acid group, a significant increase was observed in the exercise group (P = 0.04), healthy, hyaluronic acid + exercise (P = 0.001). The hyaluronic acid + exercise group had a significant increase compared to the exercise group (P = 0.001) (Figure 2).
Conclusion: The results of this study show that hyaluronic acid injection in osteoarthritis rats is associated with decreased expression of MURF-1 in gastrocnemius muscles. However, hyaluronic acid has no effect on MYOD expression. This result suggests that hyaluronic acid, by inhibiting MURF-1 expression, has the potential to inhibit skeletal muscle atrophy and, on the other hand, has no role in altering MYOD expression and muscle building. Because MYOD is a key protein in regulating muscle differentiation, it is essential for the initiation of muscle hypertrophy signaling and the activation and proliferation of satellite cells (12). To date, the role of hyaluronic acid in the signaling pathway of muscle building in osteoarthritis has not been studied, but, it is worth noting that the injection of hyaluronic acid into the injured knee joint in the treatment of osteoarthritis, is a collective agreement that has been reported in studies (17,18). Hyaluronic acid is part of the natural composition of cartilage and plays an important role in the viscoelasticity and lubrication of synovial and articular fluid and is one of the physiological factors of cartilage growth (12). Mechanism of action of hyaluronic acid through the number of living chondrocytes, creating repair thickness on the surface of cartilage, prevention of nitric oxide production in synovial and meniscus fluid, inhibition of chondrocyte apoptosis, decreased expression of metalloproteinase-3 (MMP-3) and interleukin-1-beta (IL-1β) in synovial fluid (12). Studies have also reported that the effect of hyaluronic acid on osteoarthritis may be associated with its protective effect on cartilage by inhibiting the expression of PPAR- ϒ gene. In this regard, it is stated that animals treated with hyaluronic acid showed lower expression of PPAR- ϒ than the saline group (19). Therefore, by improving the mobility of the knee joint, the possibility of muscle activity and mediation of the interventions of the muscle building pathway is provided. In the present study, aerobic exercise at 18 m/min was associated with decreased MURF-1 expression and increased MYOD expression in the injured gastrocnemius muscle. Consistent with the results of the present study, eight weeks of endurance training prevented atrophy and reduced rodent muscle volume by inhibiting the expression of the MURF-1 gene (20). A similar result was shown in the study of Agha Ali Nejad et al. In this study, resistance exercise for four weeks in diabetic rats was prevented by inhibiting MURF-1 gene expression of skeletal muscle atrophy (22). Also, in the combined groups of hyaluronic acid and exercise, each of these therapies had a synergistic effect on the expression of MURF-1 gene. Biological factors such as age and inflammatory and metabolic status of the samples seem to affect the signal pathway and markers of atrophy and muscle building, in which there are still many ambiguities, the need for further extensive studies is felt.
According to the results of this study, hyaluronic acid and moderate-intensity exercise can interfere with the expression of MURF-1, MYOD mRNA of the injured gastrocnemius muscle. Therefore, by inhibiting atrophy, they may play an important role in improving muscle building in osteoarthritis rats.