Alleviation of Papain-Induced Osteoarthritis by Recombinant Human Endostatin via Downregulation of Matrix Metalloproteinase-13, Interleukin-1 and Interleukin-6 in Rats

Osteoarthritis (OA) is a degenerative disease of joints commonly occurring in the elderly and middleaged people. This study aimed to investigate the effect of recombinant human endostatin (rhEndo) on OA and the levels of MMP-13, IL-1 and IL-6 in the synovial fluid in osteoarthritis rats. OA models were made by injecting 4% papain into the knee joint cavity of rats once every three days for three times. The models were then injected subcutaneously with rhEndo and examined six weeks later for the Mankin scores and levels of MMP-13, IL-1 and IL-6 using ELISA. Compared with control, the Mankin score as well as the levels of IL-1, IL-6 and MMP-13 were significantly increased in the models (0.30 vs. 5.80, 1.12 vs. 12.84 pg/ mL, 12.22 vs. 43.82 pg/ mL and 0.23 vs. 26.31 ng/ mL). Following treatment with 4 mg/kg rhEndo, the Mankin score in model decreased to 0.90, meanwhile, the levels of IL-1, IL-6 and MMP-13 decreased significantly to 0.79 pg/ mL, 2.89 pg/mL and 1.17 ng/mL, respectively, in a dose dependent manner. Therefore, rhEndo can alleviate osteoarthritis by reducing MMP-13, IL-1 and IL-6 expression in rats.

Synovial chondromatosis combine with synovial tuberculosis of knee joint: a case report

Backgroud Synovial chondromatosis is a rare synovial-derived metaplasia disease that comes from the formation of cartilage nodules within the synovial connective tissue of the joint. Knee tuberculosis is a disease caused mostly by the pulmonary tuberculosis and a few by tuberculosis of the digestive tract and lymphatic. tube. Case presentation Herein we report a 3-year-old child admitted by intermittent swelling of left knee joint with lameness for half a year, the patient received surgical treatment. The loose bodies filled in the joint cavity was taken out and the degenerative synovium was excised. Biopsy confirmed as synovial chondromatosis combined with synovial tuberculosis of knee joint. After 6 months follow-ups, knee swelling and claudication get totally recovered and the gait of patient recover back to normal. Conclusion Careful investigation of children with knee pain is recommended to avoid misdiagnosis, Synovial chondromatosis combine with tuberculosis should be considered a differential diagnosis in a child with knee pain.

Diagnosis and treatment of hygroma of the wrist joint in the practice of an outpatient surgeon

Introduction. Synovial cyst or hygroma is a common disease that occurs in both children and adults, but it is most often observed in people 20–45 years old. More than 60% of patients who go to the polyclinic with complaints about the presence of tumor-like formations have hygroma.Goal. Analysis of the results of treatment of synovial cysts of the hand and wrist joint according to our own observations and literature data.Material and methods. We observed 54 patients suffering from hygroma of the hand and wrist joint, who were treated in polyclinic No. 2 and MEDEL multidisciplinary clinic in Kazan from 2005 to 2020. The treatment of hygrom was carried out using conservative (puncture) and surgical methods. Results. Our experience showed that after a single puncture of the hygroma with the evacuation of its contents (10 patients), relapse developed in all cases. After repeated puncture of the hygroma in 10 patients with evacuation of the contents and subsequent administration of 0.5 ml of betaspan solution, 6 of them did not relapse within 5–6 months, but 4 patients had a relapse in the nearest period (1–2 months). Of the 23 patients who underwent surgery to remove the hygroma, 15 of them had no relapses. In 8 patients in the postoperative period, recurrent hygroma occurred, which could be explained by the ineffectiveness of eliminating the communication zone between the hygroma and the joint.Conclusions. For the successful treatment of this disease, it is important to understand that for the occurrence and development of hygroma, its communication with the joint cavity or tendon vagina is of great importance. In the absence of a message, the successful use of puncture methods of treatment is possible. In the presence of such a message and its detection during preoperative examination, surgical treatment should be planned with mandatory ligation of the leg of the hygroma.

Targeting chondrocytes for arresting bony fusion in ankylosing spondylitis

Bony fusion caused by pathological new bone formation manifests the clinical feature of ankylosing spondylitis (AS). However, the underlying mechanism remains elusive. Here we discovered spontaneous kyphosis, arthritis and bony fusion in mature CD4-Cre;Ptpn11f/f mice, which present the pathophysiological features of AS. A population of CD4-Cre-expressing proliferating chondrocytes was SHP2 deficient, which could differentiate into pre-hypertrophic and hypertrophic chondrocytes. Functionally, SHP2 deficiency in chondrocytes impeded the fusion of epiphyseal plate and promoted chondrogenesis in joint cavity and enthesis. Mechanistically, aberrant chondrocytes promoted ectopic new bone formation through BMP6/pSmad1/5 signaling. It is worth emphasizing that such pathological thickness of growth plates was evident in adolescent humans with enthesitis-related arthritis, which could progress to AS in adulthood. Targeting dysfunctional chondrogenesis with Smo inhibitor sonidegib significantly alleviated the AS-like bone disease in mice. These findings suggest that blockade of chondrogenesis by sonidegib would be a drug repurposing strategy for AS treatment.

cis-Aconitic Acid, a Constituent of Echinodorus grandiflorus Leaves, Inhibits Antigen-Induced Arthritis and Gout in Mice

cis-Aconitic acid is a constituent from the leaves of Echinodorus grandiflorus, a medicinal plant traditionally used in Brazil to treat inflammatory conditions, including arthritic diseases. The present study aimed to investigate the anti-arthritic effect of cis-aconitic acid in murine models of antigen-induced arthritis and monosodium urate-induced gout. The possible underlying mechanisms of action was evaluated in THP-1 macrophages. Oral treatment with cis-aconitic acid (10, 30, and 90 mg/kg) reduced leukocyte accumulation in the joint cavity and C-X-C motif chemokine ligand 1 and IL-1β levels in periarticular tissue. cis-Aconitic acid treatment reduced joint inflammation in tissue sections of antigen-induced arthritis mice and these effects were associated with decreased mechanical hypernociception. Administration of cis-aconitic acid (30 mg/kg p. o.) also reduced leukocyte accumulation in the joint cavity after the injection of monosodium urate crystals. cis-Aconitic acid reduced in vitro the release of TNF-α and phosphorylation of IκBα in lipopolysaccharide-stimulated THP-1 macrophages, suggesting that inhibition of nuclear factor kappa B activation was an underlying mechanism of cis-aconitic acid-induced anti-inflammatory effects. In conclusion, cis-aconitic acid has significant anti-inflammatory effects in antigen-induced arthritis and monosodium urate-induced arthritis in mice, suggesting its potential for the treatment of inflammatory diseases of the joint in humans. Additionally, our findings suggest that this compound may contribute to the anti-inflammatory effect previously reported for E. grandiflorus extracts.

Dexmedetomidine Alleviates Hyperalgesia in Arthritis Rats Through Inhibition of the p38MAPK Signaling Pathway

Background: Dexmedetomidine (DEX) has showed significant analgesic effects in neuropathic pain, but the underlying mechanism has remained elusive. Our present study aimed to explore the effect of DEX on hyperalgesia with the involvement of p38MAPK signaling pathway a rat model of monoarthritis (MA).Methods: MA rat model was induced by injection of Complete Freund's Adjuvant (CFA). Pathological changes of ma rats were observed by HE staining and Safranin-O/Fast Green staining. Ankle circumference, paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) was measured to judge the degree of hyperalgesia in MA rats. Immunohistochemistry and ELISA were applied to observe the degree of inflammation in rats. Western blot analysis was conducted to detect expression of p38MAPK signaling pathway-related factors. The mechanism of p38MAPK signaling pathway in MA rats was observed via treatment of Anisomycin or SB203580 combined with DEX.Results: After 8 h of CFA induction, joint swelling and hyperalgesia occurred in rats. There were obvious pathological changes in the joint cavity, the joint cavity space became narrow and synovial bursa became rough. A large number of inflammatory cell infiltration was observed under microscope. After injection of DEX and SB203580, PWT and PWL was prolonged, the expression of serum inflammatory factors was decreased, and the expression of p38MAPK signaling pathway-related factors was decreased; while all the detected indexes were recovered in MA rats after treated with DEX and Anisomycin.Conclusions: Our study provided evidence that DEX could alleviate hyperalgesia in arthritis rats through inhibition of the p38MAPK signaling pathway.

To the question of articular chondromatosis

Chondromatosis is a rare disease related to the pathology of the joint capsule, and is characterized by the fact that inside the joint cavity we find formations of various sizes, irregular round shape of tumor nodes, lying freely, sometimes on legs emanating from the synovium. These formations disfigure the shape of the joint and often cause a sharp restriction of mobility, sometimes bringing the range of motion to a minimum.

Arthroscopic removal of multiple foreign bodies in the knee: A case report

We report the uncommon case of knee arthroscopic removal of multiple bullet pellets. A 25-year-old male professional footballer was admitted with left knee swelling, pain, and limitation of movement following a gunshot injury. Radiographs revealed multiple pellets in and around the left knee, each measuring about 5 mm in diameter. There were several pellets in the subcutaneous, intramuscular, and intra-articular parts of the left knee. The pellets were metallic, contraindicating magnetic resonance imaging to assess intra articular structures. He was booked for an urgent knee arthroscopy and the pellets were retrieved, and the other vital intra articular structures were examined. Three 5 mm diameter spherical bullet pellets were removed from the joint cavity. The synovial membrane was debrided, and the knee lavaged. Recovery was satisfactory with no complications. The patient was discharged to physiotherapy and followed up at 3 and 6 months after surgery. Foreign bodies in the knee are not uncommon; however, the presence of multiple bullet pellets is rare, especially in the index case of a sportsman. Its removal can be challenging, even arthroscopically. Such a procedure can result in severe complications, such as infections and joint deformities. The decision to use the arthroscopic approach requires careful deliberation regarding the status of the patient vis-a-vis the available skill and experience of the managing team.

Intra-Articular Injection of a Nanosuspension of Tetramethylpyrazine Dihydroxynaphthalenate for Stronger and Longer-Lasting Effects Against Osteoarthritis

Tetramethylpyrazine (TMP), isolated from the rhizome of the traditional Chinese medicinal plant Chuanxiong (Ligusticum wallichii Franchat) shows therapeutic efficacy against osteoarthritis. After intra-articular injection, the retention time of TMP in the joint cavity is short, which limits its treatment effect. To avoid this problem, the present study explored the preparation of a TMP nanosuspension (TMP-NS) based on hydrophobic ion pairing. TMP-NS showed a particle size of approximately 588 nm and, after intra-articular injection in rats, it had longer retention in the articular cavity, higher TMP concentrations in joints, and greater anti-osteoarthritic efficacy than TMP solution. TMP-NS didn’t cause significant inflammation at the joint. These results suggest that TMP-NS may strengthen and prolong the therapeutic efficacy of TMP against osteoarthritis without systemic toxicity.

AB0797 THE ROLE OF ULTRASOUND CRITERIA IN ASSESSING PAIN SYNDROME IN THE KNEE JOINT IN PATIENTS WITH RHEUMATOID ARTHRITIS AND OSTEOARTHRITIS

Background:Pain syndrome and pathological changes in the synovium detected by ultrasound can be early signs of various diseases of the joints [1].Objectives:the use of ultrasound criteria for changes in the synovial membrane of the joint cavity to assess the severity of pain in patients with rheumatoid arthritis (RA) and osteoarthritis (OA).Methods:The study included 36 patients with RA (32 women and 4 men aged 22 to 55 years old) and 38 patients with OA (30 women and 8 men aged 30 to 50 years old) with lesions of the knee joints. A visual analogue scale (VAS) was used to determine the severity of pain. The severity of pain in the knee when walking was at least 40 mm according to the VAS in all examined patients. Joint ultrasound examination was carried out according to the standard technique using a linear transducer with a frequency of 5–12 MHz on an Accuvix V10 ultrasound diagnostic system (Samsung Medison, South Korea). The evaluation of ultrasound changes in the upper inversion of a knee joint was carried out according to the following criteria: the severity of intra-articular effusion (1), synovial proliferation (2), local vascularization of the synovial membrane using power Doppler (3) (Table 1).Table 1.Parameters of ultrasound criteria for assessing changes in the synovial membrane of the joint cavityNormal indicators1 - width of the suprapatellar turn is 6 mm2 - thickness of the synovial membrane is 3 mm (from the anterior approach)3 - lack of vascularization lociMinimum changes1 - delamination of the suprapatellar curl leaves from 7 to 9 mm2 - thickness of the synovial membrane 3.1–4.5 mm3 - appearance of single loci of vascularization (1-2 in the Doppler field)Moderate changes1 - delamination of the leaves of the suprapatellar twist 10-14 mm2 - thickness of the synovial membrane is 4.6–6.4 mm3 - appearance of moderate (> 5) vascularization lociSevere changes1 - delamination of suprapatellar folds of more than 15 mm2 - thickness of the synovial membrane is more than 6.5 mm3 - multiple foci of vascularization (> 5, merging in places)Results:Correlations of various severity were found between pain indices according to VAS and the thickness of the synovial membrane of the knee joint (r = 0.33, p = 0.019) and the number of vascularization foci (rS = 0.29, p = 0.04) in RA patients, as well as between pain according to VAS and the severity of intra-articular effusion (r = 0.28, p <0.002) in patients with OA.The patients were divided into three groups according to the severity of pain in the knee joint: group I - 41-59 mm (12 patients with OA and 9 patients with RA), group II - 60-79 mm (16 patients with OA and 12 patients with RA), group III - 80–100 mm on the VAS scale (10 patients with OA and 15 patients with RA). Group I was dominated by OA patients with minimal changes in intra-articular effusion and local vascularization of the synovial membrane, with moderate synovial proliferation (28.6% of the total number of patients in the group). In group II patients with OA with moderate severity of intra-articular effusion and local vascularization (21.4%) and patients with RA with moderate changes in the thickness of the synovium and local vascularization (25%) were equally common. Group III was dominated by RA patients with severe synovial proliferation and moderate local vascularization (28%), as well as patients with OA with moderate intra-articular effusion (20%).Significant differences in the thickness of the synovium in patients with RA in the first and third groups were noted (H-test = 5.9, p = 0.025).Conclusion:The additional use of ultrasound criteria for changes observed in the synovial membrane of the joint cavity in patients with RA and OA can help predict pain in the knee joint. The manifestation of pain syndrome in patients with OA is most associated with the severity of synovitis in the joint, and in patients with RA - with the severity of synovial proliferation.References:[1]Sarmanova A et al. Arthritis Res Ther. 2017;19(1):281.Disclosure of Interests:None declared