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Osteoarthritis (OA) is a common degenerative disease. Its most significant pathological change is destruction of articular cartilage and the main clinical symptoms are pain and dysfunction of joints. Recent studies have shown that the expression of non-coding RNA (ncRNA) in chondrocytes can abnormally up-regulate or down-regulate and alter the activities of chondrocytes like their proliferation, migration and apoptosis, thus leading to the occurrence and development of osteoarthritis. Exosomes are extracellular vesicles with a diameter of 40-100 nm, which are secreted in intercellular fluid, act as medium of intercellular communication. They protect ncRNA, protein, lipid and other bioactive materials from enzymatic degradation by encapsulating them and transferring to sibling chondrocytes, due to their good tissue permeability. They can also improve communication between cells and regulate the activities of chondrocytes. Thus, exosomes behave like gene carriers. The ncRNA carried by exosomes can supplement or adsorb the abnormal ncRNA in chondrocytes, so as to regulate the activity of chondrocytes, and is therefore considered as a possible candidate with capabilities to repair cartilages. In this study we reviewed existing literatures related to the roles and effects of exosome miRNA, lncRNA and circRNA on osteoarthritis. We also reviewed the pathogenesis of exosome ncRNA in osteoarthritis.
RESUMO
Malignant bone tumors, one of the most common bone tumors includes osteosarcoma, Ewing's sarcoma, multiple myeloma, and metastatic bone tumors etc. These tumors are often accompanied by distant metastatic lesions at time of diagnosis, leading to low 5-year survival rates. At present, the use of biomarkers for early detection in order to facilitate early treatment are very limited. Therefore, most medical researchers are exploring the roles of exosomes in detecting malignant bone tumors. Exosomes are extracellular microvesicles secreted by different types of cells, which exist in a variety of body fluids. They are new intercellular information carriers that play important physiological roles. Current literature have reported that the RNA contained in exosomes (such as mRNA, miRNAs, lncRNAs and circRNAs) play important roles in the incidence as well as development of malignant bone tumors. However, the previous studies mostly focused on the roles of exosomal RNA in malignant bone tumor diseases, in tumor cell proliferation or apoptosis, transfers, evasion of immune surveillance and chemotherapy drug resistance etc. However, exosomal RNAs may function in the whole process of the disease progression via regulation networks. Our review of existing literature revealed that exosomal RNAs affacted the proliferation, metastasis, immune evasion and drug resistance of five common malignant bone tumors; Osteosarcoma, Ewing sarcoma, Chondrosarcoma, multiple myeloma, and metastatic bone tumors. Therefore, by elucidating on the mechanism of exosomal RNAs in the occurrence and development of malignant bone tumors, this study, could provide new ideas for early diagnosis, concomitant diagnosis, efficacy estimation (chemotherapy, radiotherapy and immunotherapy, etc.) as well as assessing the prognosis of malignant bone tumors.
RESUMO
BACKGROUND: Ischemic postconditioning protects the myocardium from ischemia/recursion injury via maintaining 3-minute acidosis initially. But its effect on the skeletal muscle remains unclear. OBJECTIVE: To dynamically measure the pH values in rat skeletal muscle after ischemia, and then to simulate acidic perfusate infusion to investigate the effect of ischemic postconditioning on ischemia/reperfusion injury. METHODS: Based on the ischemia/reperfusion injury model and ischemic postconditioning protocol in previous study, dynamic measurement of pH values in rat skeletal muscle was conducted using pH instrument at the global ischemia, ischemic postconditioning (30/30 seconds) and reperfusion period, and then the acidic perfusate equivalent to pH in ischemic postconditioning period was prepared with lactic acid and normal saline. Twenty-five healthy adult male Sprague-Dawley rats were randomly divided into sham, ischemia/reperfusion, ischemic postconditioning, lactic acid, and normal saline groups (n=5 per group). Blood samples were collected to detect lactate dehydrogenase level. The samples from gastrocnemius were harvested to calculate the wet/dry ratio, level of myeloperoxidase, and infarct size through triphenyltetrazolium chloride staining. The samples from the right tibialis anterior muscle were taken to detect the expression level of Erk1/2 in the MAPK signaling pathway by western blot assay. RESULTS AND CONCLUSION: A prolonged acidic platform was detected in the early reperfusion during ischemic postconditioning, on which the pH value was 6.81±0.133, and the duration was 2 minutes and 40 seconds. The levels of lactate dehydrogenase and myeloperoxidase as well as the wet/dry ratio in the ischemic postconditioning and lactic acid groups were significantly lower than those in the ischemia/reperfusion group (P < 0.05). Western blot assay results showed that the expression level of p-Erk in the ischemic postconditioning, lactic acid and normal saline groups was significantly higher than that in the ischemia/reperfusion group (P < 0.05). Triphenyltetrazolium chloride staining results showed that compared with the ischemia/reperfusion group, the infarct area was significantly reduced in the postconditioning and lactic acid groups (P < 0.05). These findings suggest the existence of a short acidosis during ischemic postconditioning in the early reperfusion, and acidic perfusate can simulate the ischemic postconditioning and effectively attenuate ischemia/reperfusion injury in the rat skeletal muscle via activating Erk1/2 in RISK signaling pathway.
RESUMO
BACKGROUND:Reperfusion injury salvage kinase (RISK) pathway plays an important role in protective mechanism against ischemia reperfusion injury (IRI) induced by both ischemic pre-and post-conditioning. Many researches have been carried out on RISK pathway mechanism underlying ischemic post-conditioning conferring cardioprotection against IRI;however, there is less research about its effect on IRI in the skeletal muscle. OBJECTIVE:To investigate the protective effect of an optimized protocol of ischemic post-conditioning on IRI in rat skeletal muscle and its underlying mechanism. METHODS:Eighteen male Sprague-Dawley rats were equivalently randomized into IRI, ischemic post-conditioning and control groups. Rats were given occlusion or disocclusion of the right femoral artery of the right lower limb. Subsequently, the IRI group rats were subjected to 24 hours of reperfusion;the ischemic post-conditioning group immediately given 4 cycles of 30 seconds reperfusion/30 seconds ischemia, followed by 24 hours of reperfusion;the control group given no intervention. RESULTS AND CONCLUSION:Hematoxylin-eosin staining showed that in the ischemic post-conditioning group, the morphology of muscle fibers changed little, with fewer inflammatory lesions and milder edema compared with the IRI group. The infarct size with TTC staining in the ischemic post-conditioning group was smaller than that in the IRI group. Western blot analysis revealed that the expressions of phospho-Akt and phosphorylated endothelial nitric oxide synthase-S1177 were significantly increased, but the expression of phosphorylated type endothelial nitric oxide synthase-Thr495 was much decreased in the ischemic post-conditioning group compared with the IRI group. The measurement of mitochondrial permeability transition pore opening with Ca2+induction showed that the absorbance values in the ischemic post-conditioning group were significantly lower than those in the IRI group (P<0.05). These results indicate that ischemia-reperfusion injury can be improved by applying an optimal protocol of ischemic post-conditioning in rat skeletal muscle. The underlying mechanism may be associated with the activation of RISK signaling pathway to inhibit opening of mitochondrial permeability transition pore, thereby contributing to the enhanced tolerance to IRI in rat skeletal muscle.