1. Academic Validation
  2. CoCrMo-Nanoparticles induced peri-implant osteolysis by promoting osteoblast ferroptosis via regulating Nrf2-ARE signalling pathway

CoCrMo-Nanoparticles induced peri-implant osteolysis by promoting osteoblast ferroptosis via regulating Nrf2-ARE signalling pathway

  • Cell Prolif. 2021 Dec;54(12):e13142. doi: 10.1111/cpr.13142.
Yiming Xu 1 2 Weilin Sang 1 Yiming Zhong 1 2 Song Xue 1 2 Mengkai Yang 1 2 Cong Wang 1 Haiming Lu 1 Renchun Huan 1 Xinjie Mao 1 2 Libo Zhu 1 Chuanglong He 3 Jinzhong Ma 1
Affiliations

Affiliations

  • 1 Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Shanghai Bone Tumor Institution, Shanghai, China.
  • 3 State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, China.
Abstract

Objectives: Aseptic loosening (AL) is the most common reason of total hip arthroplasty (THA) failure and revision surgery. Osteolysis, caused by wear particles released from implant surfaces, has a vital role in AL. Although previous studies suggest that wear particles always lead to osteoblast programmed death in the process of AL, the specific mechanism remains incompletely understood and osteoblast Ferroptosis maybe a new mechanism of AL.

Materials and methods: CoCrMo nanoparticles (CoNPs) were prepared to investigate the influence of Ferroptosis in osteoblasts and calvaria resorption animal models. Periprosthetic osteolytic bone tissue was collected from patients who underwent AL after THA to verify osteoblast Ferroptosis.

Results: Our study demonstrated that CoNPs induced significant Ferroptosis in osteoblasts and particles induced osteolysis (PIO) animal models. Blocking Ferroptosis with specific inhibitor Ferrostatin-1 dramatically reduced particle-induced Ferroptosis in vitro. Moreover, in osteoblasts, CoNPs significantly downregulated the expression of Nrf2 (nuclear factor erythroid 2-related factor 2), a core element in the antioxidant response. The overexpression of Nrf2 by siKeap1 or Nrf2 activator Oltipraz obviously upregulated antioxidant response elements (AREs) and suppressed Ferroptosis in osteoblasts. Furthermore, in PIO animal models, the combined utilization of Ferrostatin-1 and Oltipraz dramatically ameliorated Ferroptosis and the severity of osteolysis.

Conclusions: These results indicate that CoNPs promote osteoblast Ferroptosis by regulating the Nrf2-ARE signalling pathway, which suggests a new mechanism underlying PIO and represents a potential therapeutic approach for AL.

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