ABSTRACT
To clarify the mechanisms of altered bone repair in the diabetic state, we investigated RANK, RANKL and OPG expression by immunohistochemistry and RT-PCR in the fracture sites of rats that were either healthy or made diabetic by alloxan. Histomorphometric analysis of the fracture site at 7 days after fracture revealed that diabetic rats (db) have significantly less hard tissue formation at the fracture site, compared to controls. The number of RANK, RANKL and OPG positive cells was decreased in the db group; however, the RANKL/OPG ratio was similar in controls and db at this time. At day 14, numbers of RANKL and OPG positive cells and the mRNA expression for these markers were higher in the control group than in db (P = 0.008). The RANKL/OPG ratio in the db group was greater than in controls. Our results demonstrate an imbalance of RANKL/OPG expression associated with diabetes that may contribute to the delay of fracture repair during the course of diabetes.
Subject(s)
Diabetes Mellitus, Experimental/metabolism , Osteoprotegerin/metabolism , RANK Ligand/metabolism , Receptor Activator of Nuclear Factor-kappa B/metabolism , Tibial Fractures/metabolism , Tibial Fractures/pathology , Alloxan/pharmacology , Animals , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/genetics , Gene Expression Regulation , Immunohistochemistry , Male , Osteoprotegerin/genetics , RANK Ligand/genetics , Rats , Rats, Wistar , Receptor Activator of Nuclear Factor-kappa B/genetics , Tibial Fractures/geneticsABSTRACT
Life-prolonging antiretroviral therapy remarkably reduces viral load, but it does not eradicate the virus. An important obstacle preventing virus clearance is the presence of latent virion reservoirs in the host. However, new promising antiviral approaches are emerging, and a number of host cell factors involved in the disease progression and control of HIV-1 replication have been recently discovered. For instance, the RNA interference (RNAi) mechanism, besides many functions conserved throughout evolution, works as a defence mechanism against noxious transcripts which may provide a new tool to block viral replication. The recent definition of basic RNAi mechanisms, as well as the discovery of micro RNAs (microRNAs) encoded by the host cell genome and by HIV-1, also suggest that RNAi may be involved in the control of HIV replication.
