Theranostics 2019; 9(24):7140-7155. doi:10.7150/thno.35988

Research Paper

Acetyl-11-keto-β-boswellic acid attenuates titanium particle-induced osteogenic inhibition via activation of the GSK-3β/β-catenin signaling pathway

Longbin Xiong1,2*, Yu Liu1*, Feng Zhu1*, Jiayi Lin1*, Dongxiang Wen1,2, Zhen Wang3, Jiaxiang Bai1, Gaoran Ge1, Congxin Xu1, Ye Gu4, Yaozeng Xu1✉, Jun Zhou1✉, Dechun Geng1✉

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

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
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

File import instruction

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-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