Oxidative stress induced by long-term glucocorticoid (GC) use weakens the repair capacity of bone tissue. Nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase (NOX) is a superoxide-generating enzyme that plays an important role in regulating bone metabolism. To clarify the role of nonphagocytic NOX isoforms in osteoblast reactive oxygen species (ROS) generation and apoptosis, dexamethasone was used to establish a high-dose GC environment in vitro. A dose-dependent increase in intracellular ROS generation was demonstrated, which was accompanied by increased osteoblastic MC3T3-E1 cell apoptosis. Addition of the ROS inhibitor NAC (N-acetyl-L-cysteine) or NOX inhibitor DPI (diphenyleneiodonium) reversed this effect, indicating that NOX-derived ROS can induce osteoblast apoptosis under high-dose dexamethasone stimulation. NOX1, NOX2, and NOX4 are NOX homologs recently identified in bone tissue. To clarify the NOX isoforms that play a role in osteoblast ROS generation, Nox1, Nox2, and Nox4 mRNA expression and NOX2 and NOX4 protein expression were analyzed. Nox1 and Nox4 mRNA expression was elevated in a dose-dependent manner after culture in 100 nM, 250 nM, 500 nM, or 1000 nM dexamethasone, and the increased expression of NOX1 mRNA was more significant compared with NOX4 mRNA. Small interfering RNAs (siRNAs) were used to confirm the role of NOX1 and NOX4 in ROS generation. To clarify the signaling pathway in ROS-induced osteoblast apoptosis, mitogen-activated protein kinase (MAPK) signaling molecules were analyzed. Phosphorylated ASK1 and p38 levels were significantly higher in the 1000 nM dexamethasone group, which NAC or DPI markedly attenuated. However, the total mRNA and protein levels of ASK1 and p38 between the dexamethasone group and control were not significantly different. This is related to ROS regulating the posttranslational modification of ASK1 and p38 in MC3T3-E1 cell apoptosis. Altogether, NOX1- and NOX4-derived ROS plays a pivotal role in high-dose dexamethasone-induced preosteoblast apoptosis by increasing phosphorylated ASK1 and p38 and may be an important mechanism in steroid-induced avascular necrosis of the femoral head (SANFH).
To investigate the effect and mechanism of Glucocorticoids (GCs) induced oxidative stress and apoptosis on necrosis of the femoral head in patients and rats.Methods: Eight patients with steroid-induced avascular necrosis of the femoral head (SINFH) and eight patients with developmental dysplasia of the hips (DDH) were enrolled in our study. In animal model, twenty male Sprague-Dawley rats were randomly divided into two groups (SINFH group and NS group). The SINFH model group received the methylprednisolone (MPS) injection, while control group was injected with normal saline (NS). MRI was used to confirm SINFH rat model was established successfully. Then, the rats were sacrificed 4 weeks later and femoral head samples were harvested. Histopathological staining was preformed to evaluate osteonecrosis. TUNEL staining was performed with 8-OHdG and DAPI immunofluorescence staining to evaluate oxidative injury and osteocyte apoptosis. Immunohistochemistry staining was used to detect Nox1, Nox2, and Nox4 protein expression.Results: MRI showed signs of typical osteonecrosis of femoral head in SIHFH patients. Histopathological staining showed that the rate of empty lacunae in SINFH patients was significantly higher (56.88% AE 9.72% vs 19.92% AE 4.18%, T = À11.04, P < 0.001) than that in DDH patients. The immunofluorescence staining indicated that the TUNEL-positive cell and 8-OHdG-positve cell in SINFH patients were significantly higher (49.32% AE 12.95% vs 8.00% AE 2.11%, T = À7.04, P = 0.002, 54.6% AE 23.8% vs 9.75% AE 3.31%, T = À4.17, P = 0.003) compared to the DDH patients. The immunohistochemistry staining showed that the protein expression of NOX1, NOX2 and NOX4 in SINFH patients were significantly increased (64.
Consumers are always influenced by external information before making decisions to purchase energy-saving electric appliances. However, the effects of different information sources are overlooked by previous studies. As a kind of green and safe appliance, the Heat Pump Water Heater (HPWH) is expected to be popular in the Chinese market. This study, based on an investigation in eastern China, will reveal the attitudes of potential consumers to HPWHs and verify the effects of different information sources. The results show that official information (Information from enterprises and governments) can arouse consumers’ positive attitudes toward HPWHs, yet can significantly reduce perceived usefulness among consumers, while unofficial information (Information from relatives and friends) negatively affects their attitudes. Although HPWHs are billed as energy-saving and eco-friendly appliances, consumers can obtain different information from online or offline interpersonal communications to obtain user feedback (which might be negative) before purchase. Some suggestions are proposed to promote energy-saving appliances.
Rationale:Sclerosing osteomyelitis of Garré is a rare condition that occurs most commonly in tubular bones and the mandible. Its nontypical symptoms, low morbidity, and insidious process make its diagnosis difficult at an early stage. In this article, we reported a case of chronic sclerosing osteomyelitis which occurred in flat bone.Patient concerns:A 53-year-old man was diagnosed with rib sclerosing osteomyelitis of Garré who had an 8-year course of intermittent local pain and swelling, which radiated toward the left side of his chest wall. Chest computed tomography (CT) showed irregular sclerosis of the diaphysis of the 10th rib, with periosteal reaction and narrowing of the medullary cavity, and magnetic resonance imaging (MRI) showed T2 heterogeneous low-signal intensity over the 10th rib.Diagnoses:Based on the features of the clinical signs and radiography and biopsy of the lesion, diagnosis of rib sclerosing osteomyelitis of Garré was made.Interventions:The patient was treated with surgical excision of a 10-cm-long lesion after failed conservative treatment.Outcomes:Postoperatively, the patient achieved good functional recovery at the 10-year follow-up.Lessons:Rib sclerosing osteomyelitis of Garré is an unusual condition and represents a noninfective course in the rib with a low morbidity. The surgical management was successful in relieving the patient's symptom.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.