ABSTRACT
Actin-binding proteins (ABPs) are important components of the F-actin cytoskeleton and affect the dynamics of F-actin by promoting the polymerization and depolymerization of actin. Numerous studies have shown that F-actin and actin-binding proteins are involved in all stages of carcinogenesis. Our analysis of esophageal carcinoma proteomic data showed that the actin-binding protein EHD2 (E p s l 5 homology domain-containing protein 2) is expressed at low levels in esophageal squamous cell carcinoma tissues and patients with lower EHD2 expression had poorer prognosis. Previous studies have revealed that EHD2 is involved in the regulation of glucose metabolism, autophagy and tumor cell migration. However, the role and mechanism of EHD2 in esophageal squamous cell carcinoma progression remain unclear. This study aimed to explore the effect of EHD2 on the proliferation of esophageal squamous cell carcinoma. Immunofluorescence and cell fractionation analysis showed that EHD2 was not only localized in the cell membrane and cytoplasm, but also in the nucleus. Colony formation, EdU labeling and flow cytometry were used to determine the effect of EHD2 on the proliferation of esophageal squamous cell carcinoma. The results showed that overexpression of EHD2 and EHD2-3×NLS (nuclear localization signal) inhibited proliferation, cell cycle G
ABSTRACT
Insulin-like growth factor-1 receptor (IGF-1R) is involved in both glucose and bone metabolism. IGF-1R signaling regulates the canonical Wnt/β-catenin signaling pathway. In this study, we investigated whether the IGF-1R/ β-catenin signaling axis plays a role in the pathogenesis of diabetic osteoporosis (DOP). Serum from patients with or without DOP was collected to measure the IGF-1R level using enzyme-linked immunosorbent assay (ELISA). Rats were given streptozotocin following a four-week high-fat diet induction (DOP group), or received vehicle after the same period of a normal diet (control group). Dual energy X-ray absorption, a biomechanics test, and hematoxylin-eosin (HE) staining were performed to evaluate bone mass, bone strength, and histomorphology, respectively, in vertebrae. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to measure the total and phosphorylation levels of IGF-1R, glycogen synthase kinase-3β (GSK-3β), and β-catenin. The serum IGF-1R level was much higher in patients with DOP than in controls. DOP rats exhibited strikingly reduced bone mass and attenuated compression strength of the vertebrae compared with the control group. HE staining showed that the histo-morphology of DOP vertebrae was seriously impaired, which manifested as decreased and thinned trabeculae and increased lipid droplets within trabeculae. PCR analysis demonstrated that IGF-1R mRNA expression was significantly up-regulated, and western blotting detection showed that phosphorylation levels of IGF-1R, GSK-3β, and β-catenin were enhanced in DOP rat vertebrae. Our results suggest that the IGF-1R/β-catenin signaling axis plays a role in the pathogenesis of DOP. This may contribute to development of the underlying therapeutic target for DOP.
ABSTRACT
Insulin-like growth factor-1 receptor (IGF-1R) is involved in both glucose and bone metabolism. IGF-1R signaling regulates the canonical Wnt/β-catenin signaling pathway. In this study, we investigated whether the IGF-1R/ β-catenin signaling axis plays a role in the pathogenesis of diabetic osteoporosis (DOP). Serum from patients with or without DOP was collected to measure the IGF-1R level using enzyme-linked immunosorbent assay (ELISA). Rats were given streptozotocin following a four-week high-fat diet induction (DOP group), or received vehicle after the same period of a normal diet (control group). Dual energy X-ray absorption, a biomechanics test, and hematoxylin-eosin (HE) staining were performed to evaluate bone mass, bone strength, and histomorphology, respectively, in vertebrae. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to measure the total and phosphorylation levels of IGF-1R, glycogen synthase kinase-3β (GSK-3β), and β-catenin. The serum IGF-1R level was much higher in patients with DOP than in controls. DOP rats exhibited strikingly reduced bone mass and attenuated compression strength of the vertebrae compared with the control group. HE staining showed that the histomorphology of DOP vertebrae was seriously impaired, which manifested as decreased and thinned trabeculae and increased lipid droplets within trabeculae. PCR analysis demonstrated that IGF-1R mRNA expression was significantly up-regulated, and western blotting detection showed that phosphorylation levels of IGF-1R, GSK-3β, and β-catenin were enhanced in DOP rat vertebrae. Our results suggest that the IGF-1R/β-catenin signaling axis plays a role in the pathogenesis of DOP. This may contribute to development of the underlying therapeutic target for DOP.
Subject(s)
Aged , Animals , Female , Humans , Male , Middle Aged , Rats , Bone Density , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Type 2/complications , Osteoporosis/etiology , Receptor, IGF Type 1/physiology , Signal Transduction , Streptozocin , beta Catenin/physiologyABSTRACT
BACKGROUND: Chinese medicine is effective for preventing and treating glucocorticoid-induced osteoporosis, however, the underlying mechanism remains unclear. DKK1, an inhibitor of Wnt/β-catenin signaling pathway, can be up-regulated by glucocorticoid. Thereafter, DKK1 is an important target in the prevention and treatment of osteoporosis. OBJECTIVE: To explore the regulatory effect of Zuogui pill on DKK1 in the prevention and treatment of glucocorticoid-induced osteoporosis. METHODS: Eighteen three-month-old female Sprague-Dawley rats were randomly divided into three groups: control group, model group and Zuogui pill group. Rats in the model and Zuogui pill groups received the subcutaneous injection of dexamethasone to establish the model of glucocorticoid-induced osteoporosis. The Zuogui pill group rats were administrated Zuogui pill extracts, and the control rats were given the same volume of normal saline. At 1 month after modeling, the lumbar vertebrae were removed to test the bone mass and microstructures by micro-CT scanning. The biomechanical properties were detected by compression test. The mRNA expression levels of DKK1, Runx2 and CTSK were determined by Qpcr. The serum alkaline phosphatase activity was tested. RESULTS AND CONCLUSION: Compared with the control group, in the model group, the volumetric bone mineral density, trabecular bone volume fraction, trabecular number, and trabecular thickness were significantly decreased (P ＜ 0.05), the trabecular separation and structure model index were significantly increased (P ＜ 0.05). The serum alkaline phosphatase activity was on a decline. The mRNA expression level of DKK1 showed a significant up-regulation (P ＜ 0.05). The mRNA expression level of Runx2 showed a down-regulated trend while mRNA expression level of CTSK showed an up-regulated trend. Compared with the model group, the Zuogui pill group showed significantly enhanced volumetric bone mineral density, trabecular bone volume fraction, and trabecular number (P ＜ 0.05); the structure model index was significantly decreased (P ＜ 0.05); the trabecular separation was reduced; the serum alkaline phosphatase activity was enhanced; the mRNA expression level of DKK1 showed a significant down-regulation (P ＜ 0.05); the mRNA expression level of Runx2 showed an up-regulated trend while mRNA expression level of CTSK showed a down-regulated trend. The vertebral compressive strength in the Zuogui pill group was significantly higher than that in the model group (P＜0.05). In summary, Zuogui pill prevents and treats glucocorticoid-induced osteoporosis possibly through the down-regulation of mRNA expression of DKK1.
ABSTRACT
<p><b>OBJECTIVE</b>To identify risk factors associated with patients suffered multiple level osteoporosis vertebral compression fractures(OVCFs).</p><p><b>METHODS</b>From March 2011 to March 2015, 199 patients suffered osteoporotic were classified into multiple level OVCFs group and single level OVCF group. Multivariate logistic regression analysis were performed to identify risks factors associated with multiple level OVCFs.</p><p><b>RESULTS</b>All the patients underwent OVCF, including 71 multiple level OVCFs and 128 single level OVCF. There were no differences in the age, gender, BMI, hypertension and diabetes between two groups. While multiple level OVCFs were associated with spinal deformity index SDI[(2<=SDI<4, OR=2.587, 95% CI(1.148, 5.828);SDI>=-4, OR=7.775, 95% CI(3.272, 18.478)], BMD[(T<-4.5SD, OR=2.608, 95% CI(1.038, 6.551)].</p><p><b>CONCLUSIONS</b>SDI and BMD might be the risk factors for multiple level OVCFs.</p>
ABSTRACT
<p><b>OBJECTIVE</b>To explore the clinical efficacy of delayed open reduction and internal fixation with minimally invasive percutaneous locking compression plate for the treatment of type II and III Pilon fractures.</p><p><b>METHODS</b>From January 2007 to September 2009, 32 patients with type II and III Pilon fractures were treated with open reduction and anatomic plate fixation (AP group) and minimally invasive percutaneous locking compression plate osteosynthesis (LCP group). There were 11 males and 6 females in AP group, with an average age of (37.4 +/- 13.3) years (ranged, 19 to 55 years). And there were 10 males and 5 females in LCP group, with an average age of (34.6 +/- 11.3) years(ranged, 21 to 56 years). The operating time, fracture healing time, aligned angulation and ankle function were compared between the two groups.</p><p><b>RESULTS</b>All the patients were followed up, and the during ranged from 12 to 25 months, with a mean of (15.0 +/- 1.7) months. The average operation time was (76.5 +/- 8.3) min for AP group and (58.3 +/- 3.4) min for LCP group; the average time of fracture healing was (20.5 +/- 0.4) weeks for AP group and (15.7 +/- 0.2) weeks for LCP group; the total angulation between anterior posterior film and lateral film was averaged (6.6 +/- 0.5) degrees for AP group and (3.6 +/- 0.2) degrees for LCP group. As to above index, the results of LCP group were better than those of AP group (P < 0.05). According to Kofoed criteria for ankle joint, the results of LCP group were better than those of AP group in ankle joint pain, wakling and ankle joint function (P < 0.05).</p><p><b>CONCLUSION</b>The method of minimally invasive percutaneous locking compression plate internal fixation is effective in the treatment of Pilon fracture with less invasion, faster bone union, more stabilized fixation, quicker recovery of ankle function and fewer complications, which is more advantaged for type II and III Pilon fractures.</p>