Metallic wear debris collected from patients induces apoptosis in rat primary osteoblasts via reactive oxygen species‑mediated mitochondrial dysfunction and endoplasmic reticulum stress

Yang,Fei; Tang,Jian; Dai,Kerong; Huang,Yan

doi:10.3892/mmr.2019.9825

Metallic wear debris collected from patients induces apoptosis in rat primary osteoblasts via reactive oxygen species‑mediated mitochondrial dysfunction and endoplasmic reticulum stress

Authors:
- Fei Yang
- Jian Tang
- Kerong Dai
- Yan Huang
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Affiliations: Shanghai Key Laboratory of Orthopedic Implant, Department of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
Published online on: January 4, 2019 https://doi.org/10.3892/mmr.2019.9825
Pages: 1629-1637
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although total hip arthroplasty is considered to be an effective surgical procedure for treating hip joint diseases, it is hindered by implant wear debris, which induces aseptic loosening. Various cell types are involved in this pathogenesis; however, the interactions between wear debris and osteoblasts, which serve a crucial role in bone formation, have not been clearly illustrated. In the present study, minor metallic wear particles were collected from the interfacial membrane around loosened implants of patients, and the biological effects of these particles on rat primary osteoblasts were then explored. The results demonstrated that metallic wear debris was able to induce the apoptosis of treated cells in a concentration‑ and time‑dependent manner. Furthermore, it was identified that reactive oxygen species (ROS) generation increased, the mitochondrial membrane potential collapsed, and the mitochondria‑caspase‑dependent and endoplasmic reticulum (ER) stress apoptotic pathways were activated following metallic wear debris application. In addition, apoptosis and associated pathways were inhibited by the use of N‑acetyl‑L‑cysteine, an antioxidant that suppresses ROS production, indicating that the ROS generation triggered ER stress, mitochondrial dysfunction and downstream cascades that contributed to cell apoptosis. These ﬁndings suggest that metallic wear debris‑induced ROS serve an important role in the apoptosis of osteoblasts. This provides a valuable insight, not only into understanding the mechanisms underlying the involvement of osteoblasts in osteolysis, but also into a potential novel therapeutic approach to treat implant aseptic loosening.

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