Inhibitory effect of acetyl-11-keto-?-boswellic acid on titanium particle-induced bone loss by abrogating osteoclast formation and downregulating the ERK signaling pathway

Wear debris-induced osteoclast accumulation around implants plays a crucial role during the progression of periprosthetic osteolysis (PPO). We have confirmed that acetyl-11-keto-?-boswellic acid (AKBA) promotes bone formation and protects against particle-induced bone destruction in vivo. However, the effect of AKBA on titanium-induced bone resorption is unknown. In this study, we detected the inhibitory effect of AKBA on titanium-induced bone erosion in vivo and used RAW264.7 cells and bone marrow macrophages (BMMs) to investigate the effect and underlying mechanism of AKBA on the differentiation and resorptive function of osteoclasts. Our findings revealed that AKBA inhibited particle-induced bone loss and osteoclast formation in vivo. Furthermore, AKBA exerted inhibitory effects on RANKL-induced osteoclastogenesis, osteoclastic ring-dependent resorption and the expression of osteoclast marker genes via the ERK signaling pathway in vitro. Our data further established the protective effect of AKBA on titanium particle-induced bone erosion from a new perspective of bone erosion prevention, strongly confirming that AKBA is an appropriate agent for protection against PPO.