Effects of Substance P on RANKL and OPG mRNA Expression in MG-63 Osteoblast-like Cells Exposed to Polyethylene Particles

Introduction: Particle induced osteolysis is the most frequent cause of aseptic loosening after total joint replacement. This in-vitro study of MG-63 osteoblast-like cells focused on the effect of the neurotransmitter substance P (SP) on receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG), two key regulators of particle-induced osteolysis. Materials and Methods: MG-63 cells were incubated with different concentration of SP (0.1, 1.0 and 10 ug/ml) and ultra-high molecular weight polyethylene particles (UHMWPE) in cell-particle ratios of 1:100 and 1:500. RNA was analyzed by quantitative SybrGreen RT-PCR. Results: SP treatment lead to a significantly decrease of RANKL mRNA expression (p<0.05) after 48 and 72 hours in cell-particle ratios of 1:100 and 1:500. Osteoprotegerin expression in MG-63 cells was increased after 48 hours and 72hours incubation with SP (p<0.05) while the cell-particle ratio was 1:100. The up-regulation of OPG was almost neutralized with the increase of the cell-particle concentration (1:500). Conclusion: These results demonstrate that the neurotransmitter SP can inhibit the RANKL mRNA expression and up-regulates the OPG gene transcripts of the particle-stimulated osteoblast-like cells. The neurotransmitter SP might be related to bone metabolism in conditions of particle-induced osteolysis.