Altered subchondral bone and articular cartilage interactions have been implicated in the pathogenesis of osteoarthritis (OA); however, the mechanisms remain unknown. Exosomes are membrane-derived vesicles that have recently been recognized as important mediators of intercellular communication. Herein, we investigated if OA subchondral bone derived exosomes alter transcriptional and bioenergetic signatures of chondrocytes. Exosomes were isolated and purified from osteoblasts of nonsclerotic or sclerotic zones of human OA subchondral bone and their role on the articular cartilage chondrocytes was evaluated by measuring the extent of extracellular matrix production, cellular bioenergetics, and the expression of chondrocyte activity associated marker genes. Exosomal microRNAs were analyzed using RNA sequencing and validated by quantitative real-time PCR and loss-of-function. In coculture studies, chondrocytes internalized OA sclerotic subchondral bone osteoblast derived exosomes and triggered catabolic gene expression and reduced chondrocyte-specific marker expression a phenomenon that is often observed in OA cartilage. RNA sequencing and miRNA profiling have identified miR-210-5p, which is highly enriched in OA sclerotic subchondral bone osteoblast exosomes, triggered the catabolic gene expression in articular cartilage chondrocytes. Importantly, we demonstrate that miR-210-5p suppresses the oxygen consumption rate of chondrocytes, altering their bioenergetic state that is often observed in OA conditions. These effects were markedly inhibited by the addition of a miR-210-5p inhibitor. Our study indicates that exosomes released by OA sclerotic subchondral bone osteoblasts plays a critical role in progression of cartilage degeneration and might be a potential target for therapeutic intervention in OA.

The mechanisms of chemoresistance and nanoparticle-based drug delivery systems for platinum drugs were detailed summarized in this review. The current combination therapy provided an effective strategy to overcome the platinum drug resistance.

This study aimed to explore the underlying mechanism of miR-375 in exacerbating osteoarthritis (OA). MiR-375 expression were upregulated in OA cartilage tissues, whereas ATG2B expression was decreased. MiR-375 targeted ATG2B 3' UTR and inhibited its expression in the chondrocytes, and then suppressed autophagy and promoted endoplasmic reticulum stress (ERs). The apoptosis rate of chondrocytes was increased after being transfected with miR-375 mimics. In vivo results further verified that inhibition of miR-375 could relieve OA-related symptoms. miR-375 can inhibit the expression of ATG2B in chondrocytes, suppress autophagy and promote the ERs. It suggests that miR-375 could be considered to be a key therapy target for OA. Differential expression analyses for mRNA and miRNA microarray datasets from ArrayExpress were performed. MiR-375 and ATG2B expressions in cartilage tissues were detected by qRT-PCR. Dual luciferase assay was applied to verify the targeting relationship between ATG2B and miR-375. In vitro, the role of miR-375 on chondrocyte autophagy and ERs was investigated by western blot and immunofluorescence. The apoptotic rate was quantified by flow cytometry. In vivo, OA mice model was established, HE and Safranin O and Fast Green staining, as well as the OARSI and modified Mankin scores, were applied to measure the OA cartilage damage severity.

Osteoarthritis (OA) had a high incidence in people over 65 years old, and there is currently no drug that could completely cure it. This study is aimed at studying the role of exosomes in regulating glutamine metabolism in the treatment of OA. First, we identified the exosomes extracted from the mouse OA model’s bone marrow mesenchymal stem cells (MSC). In vitro, compared with the control group, the cell apoptosis in the OA group increased, while the cell proliferation of the OA group was suppressed. After exosomal treatment, cell apoptosis and cell proliferation were reversed. Inflammatory factors (TNFα, IL‐6), glutamine metabolic activity‐related proteins (c‐MYC, GLS1), glutamine, and GSH/GSSG were increased in the OA group. The overexpression of c‐MYC reduced the therapeutic effect of exosomes. At the same time, we found that chondrocyte functional factors (collagen II, Aggrecan) were improved under the treatment of exosomes. However, oe‐c‐MYC reversed the therapeutic effect of exosomes. In vivo, we found that the running capacity of the mice in the OA group was reduced, and the cartilage tissue was severely damaged. In addition, TNFα, IL‐6, and chondrocyte apoptosis increased, while the metabolism of collagen II, Aggrecan, and glutamate decreased in the OA group. After exosomal treatment, the mice’s exercise capacity, tissue damage, inflammation, and chondrocyte function were improved, and glutamate metabolism was increased. This study showed that exosomes regulated the level of chondrocyte glutamine metabolism by regulating c‐MYC, thereby alleviating OA.

Osteoarthritis (OA) is a prevalent whole joint disease characterised by cartilage degradation, subchondral bone sclerosis and bone remodelling, and synovium inflammation, leading to pain, deformity, and cartilage dysfunction. Currently, there is no appropriate therapy for OA, and available treatments simply aim to reduce pain and swelling. Exosomes are membrane-bound extracellular vesicles secreted by almost all cells, receiving increasing interest because of their effect in cell-to-cell communication. Increasing evidence suggests that exosomes play an important role in cartilage physiological and pathological effects. This article reviews the potential role of exosomes in OA regenerative medicine. Special attention is given to mesenchymal stem cells-derived exosomes due to the extensive research on their cartilage repair property and their function as miRNA cargo. More investigations are needed for the effects of exosomes from synovial fluid and chondrocytes in joints. A better understanding of the mechanisms will contribute to a novel and promising therapy for OA patients. A better understanding of the role of extracellular vesicles in regenerative medicine will contribute to a novel and promising therapy for OA patients.

Objective: To investigate the clinical outcomes and the affecting factors of Judet's quadricepsplasty on the stiffness of post‐traumatic knee flexion.Methods: A retrospective survey was analyzed from June 2015 to October 2018. A total of 15 patients (eight males, seven females; mean age, 48.27 years) with extension contracture of the knee were treated by Judet's quadricepsplasty. All cases were injuries induced by fracture trauma. The mean interval between the initial procedure and quadricepsplasty was 56.2 months (range, 13–276 months). The knee range of motion (ROM) was assessed with a goniometer. The results of the procedure were analyzed by measuring the degrees of flexion of the operated knees at different time points (before, immediately after, and late postoperatively). We evaluated Hospital for Special Surgery (HSS) score, Judet's criteria, change in the degree of knee flexion, and complications.Results: All patients were followed up for 14 to 47 months, with an average of 31.53 months. The degree of flexion increased from 23.33° (range, 10°–50°) preoperatively to 107.33° (range, 100°–125°) intraoperatively, followed by a slight fall in the range of flexion in the late postoperative period, which reached an average of 95.33° (range, 60°–115°) in the last follow‐up. The knee joint function was assessed according to the Judet's criteria, eight cases (53.33%) achieved excellent results, six (40%) good, one (6.67%) fair, and zero (0.00%) poor results at final follow‐up. The long‐term excellent and good rate was 93.33%. The range of flexion of the knee during operation and at the last time of follow‐up was better than that before surgery (P < 0.001). The final flexion was significantly lower than that measured at immediate postoperative (P < 0.001). The mean postoperative HSS score for the entire group was 93.73 (range, 89–96). Fifteen excellent results were obtained according to the HSS knee score. Skin infection was seen in one patient (6.67%). There were no complications such as deep sepsis, intraoperative rupture of the quadriceps tendon, fracture of the lateral femoral condyle, skin dehiscence.Conclusion: Judet quadricepsplasty is an effective method to treat knee extension contracture and improve knee range of motion (ROM). It should be performed by an experienced orthopaedic surgeon and followed by physiotherapy with continuous passive motion (CPM). The knee ROM obtained with the surgery has an excellent long‐term effect.