The Intervention Research Of GF109203X Suppresses Polyethylene Particle- Induced Osteolysis

Backgroup:Aseptic loosening after joint replacement is mainly caused by wear particles induced osteolysis, and shorten the life of prosthesis. Previous studies found that GF109203X inhibits RANKL-induced osteoclastogenesis functional activation, which it provides a basis for the subsequent application in animal models of experimental study, and suggests that GF109203X has therapeutic potential in osteolytic disease.Objective:we established a mouse model of polyethylene (PE) particle-induced osteolysis to study the effect of GF109203X inhibition on osteoclastogenesis in vivo.Methods:C57BL/6 mice were randomly divided into four groups of six: Control group, Vehicle group, GF109203X-low group, and GF109203X-high group. Treatment for 14 days and then sacrificed, the calvaria were collected for micro-CT analysis and tartrate-resistant acid phosphatase (TRAP) staining, blood was collected from the femoral artery for detecting the expression of RANKL, OSCAR, CTX-land OPG by use of ELISA kits. The liver and the small intestines of the mice were extracted for hematoxylin and eosin-(H & E-) stained.Results:GF109203X acted in a dose-dependent manner to suppress the differentiation and functional activity of osteoclasts, reduce osteoclast formation, decrease the expression of osteoclast-associated receptor (OSCAR) and cross linked C-telopeptide of type I collagen (CTX-1), and promote the expression of osteoprotegerin (OPG). In addition, the degree of bone destruction was inhibited, bone resorption pitting and area were reduced, and the symptoms of osteolytic disease were lessened. The results showed that polyethylene particles can induce osteolysis, while GF109203X can suppress bone dissolution. Micro-CT scanning showed that BV/TV and marked reduction in the number of resorptive pits and percentage of porosity of the calvaria in Control group, GF-Low group and GF-High group compared with Vehicle group was significant in Statistical analyses (P< 0.05). Elisa detection on RANKL, OSCAR, CTX-1 and OPG also got the same conclusion.However, the apoptosis cell count in the liver and the small intestine has no statistical significance in pathology between each groups (P>0.05).Conclusions:In view of these findings, GF109203X may provide a new option for the treatment of osteolytic disease.