Effect of salmon calcitonin on RANK/RANKL/OPG osteolysis pathway in human macrophages after particle induction

Abstract

Objective To explore the effect of salmon calcitonin on the receptor activator of NF-κB/receptor activator of NF-κB ligand/osteoprotegerin (RANK/RANKL/OPG) osteolysis pathway in human macrophages after particles induction. Methods The polyethylene wear particles were extracted from the periacetabular boundary membrane tissue of a patient with hip prosthesis loosening. The optimal reaction cell concentration of human macrophages to polyethylene wear particles (with a concentration of 0.1 mg/ml) was measured by methyl thiazolyl tetrazolium (MTT) assay. Particles were used to stimulate human macrophages, while salmon calcitonin with different drug concentrations was used for intervention. They were randomly divided into five groups, with six parts in each group: Group A, control group; Group B, particle group; Group C, particle+ salmon calcitonin (10-8 mol/L) group; Group D, particle+ salmon calcitonin (10-10 mol/L) group; Group E, particle+ salmon calcitonin (10-12 mol/L) group. After cocultured for 48 hours, quantitative polymerase chain reaction (qPCR) assay was used to detect the mRNA expression of RANK, RANKL and OPG in macrophages. Results After induction with particles, Group B had a higher expression in RANK and RANKL, and lower OPG expression than Group A. After salmon calcitonin intervention, the expression of RANK and RANKL were significantly decreased, and OPG expression was significantly increased. Group B had the highest RANKL/OPG rate. After drug intervention, the RANKL/OPG rate in C, D, E group were reduced. Conclusions The particles can induce the transformation of macrophages into osteoclasts. In addition to directly inhibiting osteoclast activity, salmon calcitonin prevents macrophage from differentiating into osteoclasts through modulating RANKL/RANK/OPG signaling pathway. Key words: Calcitonin; Macrophages; Receptor activator of nuclear factor-kappa B; RANK ligand; Osteoprotegerin; Osteolysis; In vitro