ABSTRACT
Receptor activator of NF—κB ligand (RANKL), a TNF—related protein, is a key factor regulating bone metabolism. It has been well known that RANKL—mediated signaling regulates the formation, activation and survival of osteoclast in normal bone modeling and remodeling, and also plays an important role in a variety of pathologic conditions. However, there is no direct evidence about the effect of RANKL on osteoblast. Herein, we investigated whether RANKL had effect on cell proliferation in a normal human fetal osteoblastic cell line hFOB 1.19. MTT assay showed that RANKL inhibited hFOB 1.19 cells growth in a dose—dependent and time—dependent manner. Importantly, we found that RANKL induced the expression of a lncRNA, MALAT1, for the first time. Knockdown of RANK by siRNA blocked the induction of MALAT1 by RANKL. By infection with MALAT1 siRNA, MALAT1 knockdown reversed RANKL—induced cells growth inhibition and cell cycle arrest. In addition, MALAT1 also regulated OPG expression in hFOB 1.19 cells. In conclusion, RANKL, binding to its receptor RANK, inhibited cell proliferation via MALAT1 upregulation in osteoblast cells in vitro.
Subject(s)
Cell Proliferation/drug effects , Gene Expression Regulation/drug effects , Osteoblasts/cytology , Osteoblasts/metabolism , RANK Ligand/pharmacology , RNA, Long Noncoding/metabolism , Bone and Bones/metabolism , Cell Cycle/drug effects , Cell Line , Dose-Response Relationship, Drug , Gene Knockdown Techniques , Humans , In Vitro Techniques , Osteoblasts/drug effects , Osteoprotegerin/metabolism , RANK Ligand/antagonists & inhibitors , RNA, Long Noncoding/genetics , RNA, Small Interfering/pharmacology , Time Factors , Up-Regulation/drug effectsABSTRACT
The aim of this study was to analyze the clinical characteristics of diabetes mellitus patients with Burkholderia pseudomallei septicemia and evaluate strategies of diagnosis and treatment. The clinical characteristics, diagnosis, treatment, and prognosis of 39 diabetes mellitus patients with B. pseudomallei septicemia were retrospectively analyzed. Farmers, fishermen and workers were found to be high-risk groups. The clinical manifestations of patients were diverse without specific features, but mainly presented manifestations of acute fulminant septicemia, diabetic ketoacidosis, and abscesses in tissues or/and organs. Patients showed high mortality and misdiagnosis rates and were prone to relapses and long treatment duration as there are currently few effective and sensitive antibiotics for the disease. Consequently, the cost of treatment for the disease was high. Early diagnosis, a prolonged course of heavy doses of sensitive intravenous antibiotics, drainage of abscesses, intensive insulin therapy, and supportive treatment are the keys for successful management of the disease. Regular follow-ups combined with long-term blood glucose control can help reduce the disease recurrence.
