RESUMO
Diabetes mellitus (DM) has been demonstrated to accelerate the progression of osteoarthritis (OA) by largely unknown mechanisms. Studies have shown that DM dysfunctional adipocyte-derived exosomes play a crucial role in the pathogenesis of remote organ functions. The present study aimed to clarify whether and how diabetic adipocyte-derived exosomes mediate the pathological regulation of OA. We found that intraarticular injection of DM serum exosomes in the non-diabetic mice significantly exacerbated OA injury as evidenced by a rough and fractured cartilage surface as well as increased chondrocyte apoptosis, decreased mitochondrial membrane potential (â³Ψ) and increased expression of cleaved caspase-3. Mechanistic investigation identified that miR-130b-3p was significantly increased in circulating exosomes derived from DM mice and exosomes derived from HG-treated normal adipocytes, and we demonstrated that transfection of miR-130b-3p mimics significantly exacerbated the mitochondrial function of chondrocytes. Our data also indicated that miR-130b-3p impaired the â³Ψ, increased cleaved caspase-3 levels, and decreased the expression of 5'-adenosine monophosphate-activated protein kinase α1 (AMPKα1), Silent mating-type information regulation 2 homolog 1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) in chondrocytes. Pharmacologic activation of AMPKα1 using AICAR reversed the â³Ψ and catabolic responses in chondrocytes transfected with miR-130b-3p mimics. Moreover, AICAR decreased the effects of miR-130b-3p mimics on chondrocytes transfected with SIRT1-siRNA or PGC-1α-siRNA. The current study demonstrated that adipocyte-derived exosomal miR-130b-3p under DM conditions suppresses mitochondrial function in chondrocytes through targeting the AMPKα1/SIRT1/PGC1-α pathway, thus exacerbating OA injury.
RESUMO
OBJECTIVE: To compare the effects between computer-assisted and traditional cannulated screw internal fixation on treating femoral neck fracture. METHODS: The search was conducted in Embase, Pubmed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wanfang Database from the beginning to August 2020. RevMan5.4 software, which was provided by the International Cochrane Group, was used for the meta-analysis comparing the differences in operation time, intraoperative bleeding volume, fluoroscopy frequency, fracture healing time, total drilling times, Harris score, fracture healing rate, and femoral head necrosis rate between computer-assisted and traditional methods groups. RESULTS: A total of 1028 patients were included in 16 studies. Primary outcome indicators: Compared with the traditional method group, the computer-assisted group had less operative time (2RCTs, P < 0.00001; 8 non-RCTs, P = 0.009; Overall, P < 0.00001), intraoperative bleeding (1 RCTs, P < 0.00001; 9non-RCTs, P < 0.00001; Overall, P < 0.00001), femoral head necrosis rate (1 RCT, P = 0.11;7 non-RCTs, P = 0.09; Overall, P = 0.02) and higher Harris scores (1 RCT, P < 0.0001; 9 non-RCTs, P = 0.0002; Overall, P < 0.0001), and there were no significant differences in fracture healing rate between the two groups (5 non-RCTs, P = 0.17). Secondary outcomes indicators: The computer-assisted group had a lower frequency of intraoperative fluoroscopy and total number of drills compared with the traditional method group, while there was no significant difference in fracture healing time. CONCLUSION: Compared with the traditional hollow screw internal fixation on the treatment of femoral neck fracture, computer-assisted percutaneous cannulated screw fixation can shorten the operation time and improve the operation efficiency and reduce the X-ray injury of medical staff and help patients obtain a better prognosis. Therefore, computer-assisted percutaneous cannulated screw fixation is a better choice for the treatment of femoral neck fracture. Study registration PROSPERO registration number CRD42020214493.
