Forsythiaside inhibited titanium particle-induced inflammation via the NF-κB signaling pathway and RANKL-induced osteoclastogenesis and titanium particle-induced periprosthetic osteolysis via JNK, p38, and ERK signaling pathways

Wear particle-induced periprosthetic osteolysis is the primary complication of the total joint replacement; however, no conservative treatment except for reversal surgery is available for this disease. During the past decade, Chinese herbal medicines have been widely investigated to inhibit osteoclast differentiation, which may exhibit the potential to treat wear particle-induced periprosthetic osteolysis. The present study was aimed at the investigation of the effects of forsythiaside on osteocytes. The current data revealed that the forsythiaside treatment notably inhibited the titanium (Ti) particle-induced inflammation through impaired NF-B signaling, thereby inhibiting TNF- and IL-1. In addition, the in vitro study demonstrated that forsythiaside effectively prevented the RANKL-induced differentiation of osteoclasts and inhibited the expression of osteoclast-specific genes in osteoclasts via inhibition of the JNK signaling pathway. The in vivo study of Ti particle-induced implant-associated osteolysis indicated that forsythiaside could also inhibit osteoclastogenesis. In summary, forsythiaside could inhibit osteoclastogenesis and particle-induced inflammation, resulting in decreased secretion of inflammatory cytokines such as TNF- and IL-1. On the other hand, forsythiaside could inhibit RANKL-induced osteoclastogenesis and Ti particle-induced periprosthetic osteolysis via JNK, ERK and p38 signaling pathways. Both the abovementioned biofunctions of forsythiaside contributed to the implant-associated particle-induced osteolysis. Thus, forsythiaside can act as a candidate drug for the precaution of implant-associated particle-induced osteolysis.