GF109203X attenuates RANKL-induced osteoclastogenesis and suppresses osteolysis in a mouse model

Aseptic loosening after joint replacement is primarily caused by wear particle-induced osteolysis, which shortens the life of the prosthesis. Research shows that there are many osteolytic cytokines around prostheses that are loosened due to wear particles. Among these, receptor activator of nuclear factor κB ligand (RANKL) is the only factor that can directly stimulate the formation and functional activation of osteoclasts. This study aimed to inhibit the signaling path of RANKL-induced osteoclastogenesis is a promising prevention and treatment strategy for wear particle-induced osteolysis. Based on our previous research, it was confirmed that GF109203X attenuates osteoclastogenesis by inhibiting RANKL-induced osteoclast differentiation. We established a mouse model of polyethylene (PE) particle-induced osteolysis to study the effect of a protein kinase C (PKC) inhibitor on osteoclastogenesis in vivo. We found that by inhibiting the combination of RANKL and receptor activator of nuclear factor κB (RANK), which mediates the signaling paths of osteoclastogenesis, 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. This research helped clarify that GF109203X may provide a new option for the treatment of osteolytic disease.