Protective effects of sirtuin 3 on titanium particle-induced osteogenic inhibition by regulating the NLRP3 inflammasome via the GSK-3β/β-catenin signalling pathway

Kai Zheng; Jiaxiang Bai; Ning Li; Meng Li; Houyi Sun; Weicheng Zhang; Gaoran Ge; Xiaolong Liang; Huaqiang Tao; Yi Xue; Yuefeng Hao; Chen Zhu; Yaozeng Xu; Dechun Geng

Bioactive Materials (Oct 2021)

Protective effects of sirtuin 3 on titanium particle-induced osteogenic inhibition by regulating the NLRP3 inflammasome via the GSK-3β/β-catenin signalling pathway

Kai Zheng,
Jiaxiang Bai,
Ning Li,
Meng Li,
Houyi Sun,
Weicheng Zhang,
Gaoran Ge,
Xiaolong Liang,
Huaqiang Tao,
Yi Xue,
Yuefeng Hao,
Chen Zhu,
Yaozeng Xu,
Dechun Geng

Affiliations

Kai Zheng: Department of Orthopaedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, Jiangsu, 215006, PR China
Jiaxiang Bai: Department of Orthopaedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, Jiangsu, 215006, PR China
Ning Li: Department of Orthopaedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, Jiangsu, 215006, PR China
Meng Li: Department of Orthopaedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, Jiangsu, 215006, PR China; Department of Orthopaedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Lujiang Road No. 17, Hefei, Anhui, 230001, PR China
Houyi Sun: Department of Orthopaedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, Jiangsu, 215006, PR China
Weicheng Zhang: Department of Orthopaedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, Jiangsu, 215006, PR China
Gaoran Ge: Department of Orthopaedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, Jiangsu, 215006, PR China
Xiaolong Liang: Department of Orthopaedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, Jiangsu, 215006, PR China
Huaqiang Tao: Department of Orthopaedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, Jiangsu, 215006, PR China
Yi Xue: Department of Orthopaedics, Changshu Hospital Affiliated to Nanjing University of Traditional Chinese Medicine, Suzhou, Jiangsu, 215500, PR China
Yuefeng Hao: Orthopaedics and Sports Medicine Center, Suzhou Municipal Hospital (North District), Nanjing Medical University Affiliated Suzhou Hospital, No. 242 Guangji Road, Suzhou, 215006, PR China; Corresponding author.
Chen Zhu: Department of Orthopaedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Lujiang Road No. 17, Hefei, Anhui, 230001, PR China; Corresponding author.
Yaozeng Xu: Department of Orthopaedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, Jiangsu, 215006, PR China; Corresponding author.
Dechun Geng: Department of Orthopaedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, Jiangsu, 215006, PR China; Jiangsu Key Laboratory of Clinical Immunology, Soochow University, No. 708 Renmin Road, Suzhou, Jiangsu, 215007, PR China; Corresponding author. Department of Orthopaedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, Jiangsu, 215006, PR China

Journal volume & issue: Vol. 6, no. 10
pp. 3343 – 3357

Abstract

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Periprosthetic osteolysis (PPO) remains the key factor in implant failure and subsequent revision surgery and is mainly triggered by wear particles. Previous studies have shown that inhibition of osteoblastic differentiation is the most widespread incident affecting the interface of trabecular and loosening prostheses. Additionally, the NLRP3 inflammasome is activated by prosthetic particles. Sirtuin3, an NAD+-dependent deacetylase of mitochondria, regulates the function of mitochondria in diverse activities. However, whether SIRT3 can mitigate wear debris-induced osteolysis by inhibiting the NLRP3 inflammasome and enhancing osteogenesis has not been previously reported. Therefore, we investigated the role of SIRT3 during the process of titanium (Ti) particle-induced osteolysis. We revealed that upregulated SIRT3 dramatically attenuated Ti particle-induced osteogenic inhibition through suppression of the NLRP3 inflammasome and improvement of osteogenesis in vivo and in vitro. Moreover, we found that SIRT3 interference in the process of Ti particle-induced osteolysis relied on the GSK-3β/β-catenin signalling pathway. Collectively, these findings indicated that SIRT3 may serve as a rational new treatment against debris-induced PPO by deacetylase-dependent inflammasome attenuation.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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