RESUMO
The accumulation of giant lipid droplets (LDs) increases the risk of metabolic disorders including obesity and insulin resistance. The lipolysis process involves the activation and transfer of lipase, but the molecular mechanism is not completely understood. The translocation of ATGL, a critical lipolysis lipase, from the ER to the LD surface is mediated by an energy catabolism complex. Oxysterol-binding protein-like 2 (OSBPL2/ORP2) is one of the lipid transfer proteins that regulates intracellular cholesterol homeostasis. A recent study has proven that Osbpl2-/- pigs exhibit hypercholesterolemia and obesity phenotypes with an increase in adipocytes. In this study, we identified that OSBPL2 links the endoplasmic reticulum (ER) with LDs, binds to COPB1, and mediates ATGL transport. We provide important insights into the function of OSBPL2, indicating that it is required for the regulation of lipid droplet lipolysis.
RESUMO
MicroRNAs serve an important role in the development of several diseases. Numerous genes regulate the skeletal muscle differentiation of C2C12 myoblasts. The role of miR760 in rheumatoid arthritis (RA) has not been reported, to the best of our knowledge. Therefore, the aim of the present study was to examine the role of miR760 in regulating skeletal muscle proliferation in RA. Potential genes functionally involved in the tarsal joint of a collageninduced RA model were identified using Gene Expression Omnibus. Reverse transcriptionquantitative PCR and western blot analyses were performed to determine the mRNA and protein expression levels. The proliferation, cell cycle progression and migration of C2C12 myoblasts were detected using Cell Counting Kit8, flow cytometry and woundhealing assays, respectively. TargetScan was used to predict the potential target genes of miR760, and this was verified using a dualluciferase reporter assay. In the present study, myosin18b (Myo18b) expression was determined to be downregulated in the RA model. Silencing Myo18b decreased the proliferation, abrogated the cell cycle progression, and reduced the migration and differentiation of C2C12 myoblasts. Expression levels of cyclindependent kinase 2, cyclin D1, matrix metalloproteinase (MMP)2, MMP9, myogenin and myosin heavy chain 6 were all decreased when Myo18b was silenced. Furthermore, overexpression of Myo18b induced opposing effects on C2C12 myoblasts. It was shown that Myo18b was a target gene of miRNA760. Overexpression of miR760 decreased proliferation, cell cycle progression, migration and differentiation in C2C12 myoblasts, and decreased the expression of Myo18b. The opposite results were observed when miR760 was downregulated. In conclusion, miR760 inhibited proliferation and differentiation by targeting Myo18b in C2C12 myoblasts. The results of the present study may contribute to understanding the mechanisms underlying RA skeletal muscle proliferation, and miR760/Myo18b may serve as potential targets for treating patients with RA.
Assuntos
Artrite Reumatoide/genética , Mioblastos/patologia , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/patologia , Ciclo Celular , Linhagem Celular , Movimento Celular , Proliferação de Células , Colágeno , Regulação para Baixo , Camundongos , Desenvolvimento Muscular , Mioblastos/citologia , Regulação para CimaRESUMO
OBJECTIVE: To explore the surgical management and its results of intercondylar fractures of the humerus through approach of osteotomy of olecranon (AOO) with dual steel plate. METHODS: From June 2001 to March 2007, 38 patients of intercondylar fractures of humerus were treated surgically through AOO, and the fracture was reduced and fixed with dual steel plate. There were 24 males and 14 females with a mean age of 37 years (range 19 to 48 years). All cases were closed fractures. The fractures were classified according AO included 12 cases of C1, 20 cases of C2 and 6 cases of C3. The time from injured to operation was 6 hours to 14 days (means 7 days). RESULTS: These 38 patients were followed up from 5 months to 2 years (average 12 months). The wound healing of one patient was below the mark. After the treatment of change dressings, the wound healed. Of these 38 patients, no loosening or breakage of internal fixation occurred. All the osteotomies healed in 15 weeks averagely (range 12 to 22 weeks). According to Cassebaum scoring system, the results were excellent in 15 cases, good in 17 cases, fair in 5 cases and poor in 1 case. CONCLUSION: The technique of dual steel plate for the treatment intercondylar fractures of the humerus through approach of osteotomy of olecranon (AOO) offers many advantages, such as sufficient exposure easy, stable fixation and earlier exercise. Functional exercise in the early period is the crucial factor of enhancing the therapeutic effect.