Expression profile of osteoprotegerin, RANK and RANKL genes in the femoral head of patients with avascular necrosis

• Expression levels of OPG, RANKL and RANK in the femoral head of patients with AVN.
• Parallel evaluation of mRNA and protein levels in normal/necrotic sites.
• Higher OPG mRNA levels in the necrotic site.
• RANK/OPG and RANKL/OPG ratios were elevated in the necrotic samples.
• We suggest two mechanisms that could be acting against bone remodelling.

IntroductionFemoral head avascular necrosis (AVN) is a recalcitrant disease of the hip that leads to joint destruction. Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor kappa-B (RANK) and RANK ligand (RANKL) regulate the balance between osteoclasts–osteoblasts. The expression of these genes affects the maturation and function of osteoblasts–osteoclasts and bone remodeling. In this study, we investigated the molecular pathways leading to AVN by studying the expression profile of OPG, RANK and RANKL genes.Material and methodsQuantitative Real Time-PCR was performed for evaluation of OPG, RANK and RANKL expression. Analysis was based on parallel evaluation of mRNA and protein levels in normal/necrotic sites of 42 osteonecrotic femoral heads (FHs). OPG and RANKL protein levels were estimated by western blotting.ResultsThe OPG mRNA levels were higher (insignificantly) in the necrotic than the normal site (p > 0.05). Although the expression of RANK and RANKL was significantly lower than OPG in both sites, RANK and RANKL mRNA levels were higher in the necrotic part than the normal (p < 0.05). Protein levels of OPG and RANKL showed no remarkable divergence.ConclusionsOur results indicate that differential expression mechanisms for OPG, RANK and RANKL that could play an important role in the progress of bone remodeling in the necrotic area, disturbing bone homeostasis. This finding may have an effect on the resulting bone destruction and the subsequent collapse of the hip joint.