| BackgroundKnee osteoarthritis is a serious rheumatic diseases, articular cartilage damage, joint space narrowing. In severe cases, when the knee completely lost cartilage, bone and soft tissue structures around the joint will start to change, which could lead to joint pain, swelling and disability. In the United States, symptomatic knee osteoarthritis occurs in approximately 10% of adults aged 60 or over. According to recent statistics, there are 9.3 million adults suffer from osteoarthritis of the knee in the United States. The overall number of OA as high as 350 million. Average every six persons is one person suffering from the disease in Asia. The advent of the age of aging, OA patients has increased every year, estimated at around 200 million. Sick male to female ratio is 1:2. As a result of the aging process, the number of people with osteoarthritis of the knee is expected to increase in the coming decades, osteoarthritis is considered to be the fourth largest reason for disability in 2020. The purpose of the treatment of knee arthritis is to relieve pain and swelling and improve joint mobility and reduce disability. The current treatment options in several evidence-based clinical guidelines recommend including diet, exercise, oral medication, topical treatment, endovascular treatment, non-drug therapy and surgery. These different interventions, non-steroidal anti-inflammatory drugs or intra-articular application of hyaluronic acid and glucocorticoids in clinically more common. However, this in some cases, the treatment may be ineffective or lead to serious adverse events, in this case, clinicians and patients become more willing to take on complementary and alternative medicine for osteoarthritis of the knee treatment options.Chondrocytes are the only cells in articular cartilage, which is responsible for extracellular matrix synthesis and updating the matrix to maintain integrity. Apoptosis is a normal physiological process, is a gene regulation by the initiative to go unless a process of programmed cell death, whereas excessive apoptosis is pathological and harmful. Normal articular cartilage cells apoptosis, but the detection rate is low, the number of apoptosis was significantly increased in patients with osteoarthritis. Someone (Heraud) detecting the normal and OA patients, hip cartilage chondrocyte apoptosis rates were 2-5% and 18-21%; Blanco reported to be 11% and 50%; Hashimoto reported to be 6.7% and 28.7%, indicating that patients with bone and joint pathological apoptosis. Its pathologic apoptosis mainly in shallow and middle cartilage damage after these areas are nitric oxide synthase (iNOS) expression and NO highest region, but also the loss of proteoglycan most areas.Nesfatin-1 is a 82 amino acid polypeptide, is first described in 2006 by Japanese scholars oh-i and colleagues, in rats administered to the mice can induce anxiety, fear response, and reduce appetite. In addition, studies in France Bonnet et al found Nesfatin-1 and peripheral inflammatory signals are closely related. Nesfatin can be hydrolyzed into three segments, respectively Nesfatin-1, Nesfatin-2 and Nesfatin-3. But only Nesfatin-1 has a role in suppressing appetite. Initial studies found Nesfatin-1 exists only in hypothalamic neurons which, however, along with in-depth research and found that there are in the brainstem and peripheral tissues. Recent studies have found that, Nesfatin-1 can be anti-inflammatory and inhibit apoptosis, however Nesfatin-1 in inflammation in the knee has not yet been reported.ObjectiveThis study from the perspective of an animal model, and discuss changes Nesfatin-1 serum levels of inflammatory synovial cells of rat knee study the relationship with apoptosis in synovial membrane and regulate by what means, that the etiology of osteoarthritis of the knee study provides a scientific basis, to provide a new direction for the treatment of osteoarthritis of the knee.MethodsEstablishing rat model of knee arthritis by intra-articular injection of urokinase given Nesfatin-1 intervention, using immunohistochemistry, flow cytometry and western blot detection of pathological changes, inflammatory factors and endoplasmic reticulum stress and apoptosis.Results1. Rat paw swelling, joint swelling significantly thicker, limited mobility. Cartilage Pathological microscopic sections show control cells arranged in neat, uniform dyeing; OA group cell disorder, cartilage ulceration, inflammatory cell infiltration. Arthritic score OA group were in line with changes in arthritis. Rats knee diameter measurement, OA group had significantly increased.2. Compared with the Control group, OA group IL-1β. TNF-α serum concentrations of HA and has significantly increased.3. Compared with the Control group, the expression of both the OA group serological or protein concentration, Nesfatin-1 levels in comparison with the control group showed a significant decrease.4. Nesfatin-1 after the intervention, decreased apoptosis, and decreased with increasing concentration, high concentration group apoptosis rate decreased most significantly.5. caspase-3, caspase-7 and caspase-9 were detected, can be obtained, after the intervention showed a significant decline in its expression, there is a dose dependent manner, with the Nesfatin 1-increasing concentration, high concentration Histone decreased expression of the most significant.6. IL-1β, HA and TNF-a were detected, can be obtained, after the intervention significantly decreased serum concentrations, which have a concentration-dependent manner, with the Nesfatin 1-increasing concentration, high concentration of histone decreased expression of the most significant.7. After the intervention, the degree of joint swelling in rats no significant difference in the low concentration group, as the concentration increases, the degree of joint swelling decreased significantly, which is most evident at high concentrations.8. Arthritis CHOP group and GRP78 protein strongly expressed in two, with the two intervention after Nesfatin-1 protein expression was significantly decreased in a dose-dependent decrease in the high concentration group the most significant.9. detected CHOP and GRP78 expression, the expression levels of two proteins OA group was significantly higher than that, there was a statistically significant difference between the two.10. TG after stimulation of apoptosis-related protein caspase-3, the expression of caspase-7 with the control group and the comparison of caspase-9 significantly increase, and when added after the Nesfatin-1 significantly decreased expression of these three groups.Conclusion1. The intra-articular injection of urokinase in rats can be successfully induced arthritis of the knee pathological state.2.Nesfatin-1 can reduce knee arthritis inflammation pathological processes associated with reduced levels of apoptosis.3. ER stress with knee osteoarthritis.4. Mechanism of Nesfatin-1 by knee joint inflammation factor and apoptosis is inhibited the activation of endoplasmic reticulum stress. |
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