In the past decade, mesenchymal stem cells (MSCs) have been widely used for the treatment of osteoarthritis (OA), and extracellular vesicles (EVs) may play a major role in the efficacy of this treatment. Hypoxia can change the cargo and biological functions of MSC-derived EVs (MSC-EVs). The aim of the present study was to determine whether the effects of hypoxia-preconditioned MSC-EVs on OA cartilage repair are superior to normoxia-preconditioned MSC-EVs. By using in vitro and in vivo OA models, we verified that hypoxia-preconditioned MSC-EVs improved chondrocyte proliferation and migration and suppressed chondrocyte apoptosis to a greater extent than normoxia-preconditioned MSC-EVs. Furthermore, we found that hypoxia altered the microRNA expression in MSC-EVs and identified four differentially expressed microRNAs: hsa-miR-181c-5p, hsa-miR-18a-3p, hsa-miR-376a-5p, and hsa-miR-337-5p. Bioinformatics analysis revealed that hypoxic pretreatment may promote cartilage repair by stimulating chondrocyte proliferation and migration and suppressing chondrocyte apoptosis through the miRNA-18-3P/JAK/STAT or miRNA-181c-5p/MAPK signaling pathway. Therefore, hypoxia-preconditioned EVs may be a novel treatment for OA.
Elevated visceral obesity by VFA is associated with increased surgical complexity, postoperative morbidity, postoperative stay and hospitalization expenses for RCCC patients and may be superior to BMI for renal cancer outcome assessment. VFA may be a useful index for the evaluation and calculation of RCCC aggressiveness.
BACKGROUND Inflammatory cytokines play a vital role in the occurrence of osteoarticular injury and inflammation. Whether inflammation-associated factors interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) are involved in the pathogenesis of keen articular cartilage injury remains poorly understood. AIM To measure the levels of inflammatory factors [IL-1β, IL-6, TNF-α and VEGF] in patients with knee articular cartilage injury. METHODS Fifty-five patients with knee articular cartilage injury were selected as patient groups, who were divided into three grades [mild ( n = 20), moderate ( n = 19) and severe ( n = 16)] according to disease severity and X-ray examinations. Meanwhile, 30 healthy individuals who underwent physical examination were selected as the control group. The levels of IL-1β, IL-6, TNF-α and VEGF were measured by ELISA and immunohistochemical staining. RESULTS Compared with the control group, patient groups displayed significantly higher levels of IL-1β, IL-6, TNF-α and VEGF, and the extent of increase was directly proportional to the severity of injury ( P < 0.05). In addition, the number of cells with positive staining of IL-1β, IL-6, TNF-α and VEGF in the synovial membrane were significantly increased, along with increased disease severity ( P < 0.05). After treatment, the scores of visual analogue scale and the Western Ontario and McMaster University of Orthopaedic Index in patient groups were 2.26 ± 1.13 and 15.56 ± 7.12 points, respectively, which were significantly lower than those before treatment (6.98 ± 1.32 and 49.48 ± 8.96). Correlation analysis suggested that IL-1β and TNF-α were positively correlated with VEGF. CONCLUSION IL-1β, IL-6, TNF-α and VEGF levels are increased in patients with knee articular cartilage injury, and are associated with the disease severity, indicating they might play an important role in the occurrence and development of knee articular cartilage injury. Furthermore, therapeutically targeting them might be a novel approach for the treatment of keen articular cartilage injury.
Purpose:To investigate whether single femoral, single tibial tunnel anatomic double-bundle anterior cruciate ligament (ACL) reconstruction is equal to or superior to double femoral, double tibial tunnel ACL double-bundle anatomic reconstruction in terms of restoring the stability and functions of the knee joint.Methods:A prospective clinical study was performed to compare 30 cases of single-tunnel ACL double-bundle anatomic reconstruction to 28 cases of double-tunnel ACL double-bundle anatomic reconstruction, with average follow-up of 36 months. All graft tendons were hamstring tendon autografts. Tunnel placements in all the cases were made anatomically. Clinical results were collected after reconstruction. Graft appearance, meniscus status and cartilage state under arthroscopy were compared and analyzed.Results:Tunnel placements were in the anatomic positions in both groups. On the lateral pivot-shift test performed at 36 months postoperatively, there was no significant difference between groups. Clinical results such as International Knee Documentation Committee score, Tegner activity scale, and range of motion showed no significant differences between the groups. The mean thickness of anteromedial graft was reduced by 10.3% and that of the posterolateral graft was reduced by 11.1% from the original graft thickness evaluated by magnetic resonance imaging. No new meniscal tears were found either group; however, cartilage damage occurred in the double-tunnel group at 39.3%, and this rate was significantly higher than that in the single-tunnel group (10.0%).Conclusion:Single femoral, single tibial tunnel anatomic double-bundle ACL reconstruction has the same effectiveness as the double femoral, double tibial tunnel in restoring the knee's stability and functions.
Background: Some studies have reported results from the use of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) to treat osteoarthritis (OA). Objective: To evaluate the efficacy of MSC-EVs as a treatment for OA. Data sources: Databases were searched using the terms ‘mesenchymal stem cells’, ‘osteoarthritis’ and ‘extracellular vesicles.’ Study eligibility criteria: Studies performed in animal models utilizing MSC-EVs to treat OA that described the macroscopic evaluation or histological evaluation were included. Study appraisal: The quality of the studies was examined using the CAMARADES quality checklist. Results: MSC-EVs were superior to the placebo in the macroscopic evaluation and histological evaluation. MSC-EVs were more effective in the early stage of OA and once a week was better than multiple times a week. Limitations: The included studies were highly heterogeneous. Conclusion: MSC-EVs may improve the results of macroscopic and histological evaluations of OA.
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