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  2. Acetyl-11-keto-β-boswellia acid attenuates Ti particle-induced osteoblastic oxidative stress and osteolysis through the Foxo3 signaling pathway

Acetyl-11-keto-β-boswellia acid attenuates Ti particle-induced osteoblastic oxidative stress and osteolysis through the Foxo3 signaling pathway

  • Int Immunopharmacol. 2024 Dec 25;143(Pt 3):113547. doi: 10.1016/j.intimp.2024.113547.
Yingchu Gu 1 Zerui Wu 2 Heng Xie 2 Zhengtao Qian 3 Zhijie Li 1 Yihan Tang 1 Qiufei Wang 1 Tao Fang 1 Huaqiang Tao 4 Kai Chen 4 Pengfei Zhu 4 Yi Ding 5 Yaozeng Xu 4 Yuqin Peng 1 Hongwei Ye 6 Xiaobin Guo 7 Yunxia Tao 8 Ye Gu 9
Affiliations

Affiliations

  • 1 Department of Orthopedics, Central Laboratory, Changshu Hospital Affiliated to Soochow University, First People's Hospital of Changshu City, Changshu 215506, China.
  • 2 Department of Orthopedics, Central Laboratory, Changshu Hospital Affiliated to Soochow University, First People's Hospital of Changshu City, Changshu 215506, China; Department of Orthopedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou 215000, China.
  • 3 Department of Orthopedics, Central Laboratory, Changshu Hospital Affiliated to Soochow University, First People's Hospital of Changshu City, Changshu 215506, China; Department of Clinical Laboratory, Changshu Medicine Examination Institute, Changshu, Jiangsu, China.
  • 4 Department of Orthopedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou 215000, China.
  • 5 Department of Clinical Laboratory, Changshu Medicine Examination Institute, Changshu, Jiangsu, China.
  • 6 Department of Orthopedics, Central Laboratory, Changshu Hospital Affiliated to Soochow University, First People's Hospital of Changshu City, Changshu 215506, China. Electronic address: yehongwei8@126.com.
  • 7 Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, 137 South LiYuShan Road, Urumqi, Xinjiang 830054, China. Electronic address: 879885509@qq.com.
  • 8 Department of Orthopedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou 215000, China. Electronic address: taoyx8493@163.com.
  • 9 Department of Orthopedics, Central Laboratory, Changshu Hospital Affiliated to Soochow University, First People's Hospital of Changshu City, Changshu 215506, China; Department of Clinical Laboratory, Changshu Medicine Examination Institute, Changshu, Jiangsu, China. Electronic address: edwinguye@126.com.
Abstract

Oxidative stress injury in osteoblasts is one of the leading causes of periprosthetic osteolysis (PPOL). Acetyl-11-keto-β-boswellia acid (AKBA) has been used as an antioxidant in the treatment of various diseases, but its antioxidant mechanism in osteolysis has yet to be elucidated. In this study, a mouse cranial osteolysis model was constructed, and MC3T3-E1 cells and bone marrow mesenchymal stem cells (BMSCs) were cultured in vitro. Western blotting and immunofluorescence staining revealed that titanium (Ti) particles aggravated osteoblast oxidative stress injury and Apoptosis. Ti particles and hydrogen peroxide reduced the osteogenic ability of BMSCs. At a certain concentration, AKBA alleviated the oxidative stress injury of MC3T3-E1 cells induced by Ti particles and enhanced the osteogenic ability of BMSCs, and the expression of Forkhead box O3 (Foxo3) increased with increasing AKBA concentration. To verify the antioxidant mechanism of AKBA, we designed and synthesized Foxo3-targeting siRNAs. We found that after Foxo3 expression was inhibited, the protective effect of AKBA on osteoblasts decreased significantly. Moreover, AKBA treatment suppressed bone mass loss in the skull mediated by Ti particles in mice. Therefore, we suggest that AKBA alleviates the oxidative stress injury in osteoblasts induced by Ti particles, at least in part, by regulating the expression of Foxo3. In this study, the mechanism and biosafety of AKBA in treating PPOL were demonstrated to some extent.

Keywords

AKBA; Osteoblasts; Periprosthetic osteolysis; ROS; Ti particles.

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