Exosomal miR-150 derived from BMSCs inhibits TNF-α-mediated osteoblast apoptosis in osteonecrosis of the femoral head by GREM1/NF-κB signaling.

Aim: The purpose of this study was to investigate the functions of exosomal miR-150 derived from bone marrow mesenchymal stem cells in osteonecrosis of the femoral head (ONFH). Materials & methods: Cell viability and apoptosis were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. Alizarin red staining was performed to detect calcium deposits. A rat model was established to assess the effects of exosomal miR-150 on ONFH in vivo. Results: Exosomes or exosomal miR-150 derived from bone marrow mesenchymal stem cells inhibited TNF-α-induced osteoblast apoptosis and promoted osteogenic differentiation and autophagy. Exosomal miR-150 suppressed apoptosis and induced autophagy in TNF-α-treated osteoblasts by regulating the GREM1/NF-κB axis. Exosomal miR-150 also improved the pathological features of ONFH in vivo. Conclusion: Exosomal miR-150 alleviates ONFH by mediating the GREM1/NF-κB axis. This study provides a potential therapeutic strategy for ONFH.

Osteonecrosis of the femoral head (ONFH) is an orthopedic disease that frequently occurs in young adults aged less than 50 years. At present, there is no widely accepted curative surgical procedure or drug therapy for this disease. Bone marrow mesenchymal stem cells (BMSCs) play a key role in the progression of ONFH. BMSC-derived exosomes refer to small membrane vesicles that can transfer proteins, miRNAs and mRNAs, which are closely related to the development of ONFH. This study showed that exosomal miRNA-150 derived from BMSCs inhibited TNF-α-induced osteoblast apoptosis and promoted osteogenic differentiation and autophagy by regulating the GREM1/NF-κB axis. In addition, exosomal miRNA-150 alleviated the symptoms of ONFH in rats.

Influence of Liver Cirrhosis on Blood Glucose, Insulin Sensitivity and Islet Function in Mice.

BACKGROUND: The relationship between cirrhosis and diabetes is controversial. We studied the influence of cirrhosis on glucose levels and islet function and explored its possible mechanisms. MATERIALS AND METHODS: Cirrhosis was induced in male C57BL/6 mice by bile duct ligation (BDL). Serum biochemical parameters were determined, and oral glucose tolerance tests (OGTT) were performed at 4 and 8 weeks after BDL. Histopathology and phospho-NF-κB-p65/I-kappa B α immunohistochemical staining of the liver and islet were observed. The protein levels of the insulin signaling system and the gene expression of insulin-degrading enzyme (IDE) in the liver and muscle were determined. The activity of glucokinase (GCK) and glucose 6-phosphatase (G6P) and glycogen levels in liver homogenates were measured. RESULTS: After BDL, the mice developed cirrhosis, and fasting glucose decreased significantly, but 2 h postprandial glucose increased, and the insulin areas under the curves increased. At 4 weeks of BDL, the ratios of phospho-NF-κB-p65/I-kappa B α accumulation in the liver and islet increased, the activity of G6P and the glycogen content in liver homogenates decreased, the insulin signaling system and the gene expression of IDE in the liver was downregulated, and the islet areas were decreased. After 8 weeks, these changes were more severe. CONCLUSIONS: In different periods of cirrhosis, the levels of fasting glucose and 2 h postprandial glucose changed in different amplitudes. Glycogen concentrations and the activity of G6P in the liver were decreased. The mice developed insulin resistance and the islet areas were decreased. The NF-κB pathway may play a role in the process.