Theranostics 2019; 9(24):7140-7155. doi:10.7150/thno.35988
Acetyl-11-keto-β-boswellic acid attenuates titanium particle-induced osteogenic inhibition via activation of the GSK-3β/β-catenin signaling pathway
1. Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China;
2. Sun Yat-sen University Cancer Center; State key laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510000, China;
3. Department of Orthopaedics, Suzhou Kowloon Hospital Shanghai Jiao Tong University School of Medicine, Suzhou, Jiangsu 215006, China;
4. Department of Orthopedics, Soochow University Affiliated First People's, Hospital of Changshou City, Changshu, China
*Contributed equally to this work
Xiong L, Liu Y, Zhu F, Lin J, Wen D, Wang Z, Bai J, Ge G, Xu C, Gu Y, Xu Y, Zhou J, Geng D. Acetyl-11-keto-β-boswellic acid attenuates titanium particle-induced osteogenic inhibition via activation of the GSK-3β/β-catenin signaling pathway. Theranostics 2019; 9(24):7140-7155. doi:10.7150/thno.35988. Available from http://www.thno.org/v09p7140.htm
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-β-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-3β, decreased the degradation of β-catenin, and increased the translocation of β-catenin from the cytoplasm to the nucleus. Taken together, these results showed that AKBA treatment attenuated titanium-induced osteogenic inhibition by activating the GSK-3β/β-catenin signaling pathway.
Conclusion: These findings suggest that AKBA is a promising new target in the prevention and treatment of PPO.
Keywords: acetyl-11-keto-β-boswellic acid, peri-prosthetic osteolysis, titanium particle, bone formation, GSK-3β