Acetyl-11-keto-?-boswellic acid attenuates titanium particle-induced osteogenic inhibition via activation of the GSK-3?/?-catenin signaling pathway.
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ABSTRACT: Rationale: Peri-prosthetic osteolysis (PPO) is mainly induced by wear particles and represents the leading cause of implant failure and revision surgery. Previous studies have identified mitigation of wear particle-induced inflammation and bone resorption as the main approaches to treat PPO. Recently, wear particle-induced reduction of bone formation around the prosthesis was identified as a major factor in the development of PPO. Acetyl-11-keto-?-boswellic acid (AKBA), a derivative of frankincense, has been shown to play a potential role in bone metabolism. However, whether AKBA enhances bone formation in wear particle-induced osteolysis remains unknown. In this study, we examined whether AKBA attenuates titanium particle-induced osteogenic reduction. Methods: Titanium particles were used to induce osteolysis in murine calvaria, and micro-CT and histological analyses were used to evaluate the results. Mouse osteoblast cells, MC3T3-E1 were co-cultured with titanium particles to determine their effect on osteoblast formation in vitro. Results: We demonstrated that AKBA treatment significantly inhibited titanium particle-induced osteogenic inhibition by enhancing osteogenesis both in vivo and in vitro. AKBA treatment also enhanced the phosphorylation of GSK-3?, decreased the degradation of ?-catenin, and increased the translocation of ?-catenin from the cytoplasm to the nucleus. Taken together, these results showed that AKBA treatment attenuated titanium-induced osteogenic inhibition by activating the GSK-3?/?-catenin signaling pathway. Conclusion: These findings suggest that AKBA is a promising new target in the prevention and treatment of PPO.
SUBMITTER: Xiong L
PROVIDER: S-EPMC6831297 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
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