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

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.

Sensitivity of allyl isothiocyanate to induce apoptosis via ER stress and the mitochondrial pathway upon ROS production in colorectal adenocarcinoma cells

“…Consistently, our results indicated that AITC treatment increased ROS generation and the antioxidant NAC exhibited a protective effect against AITC. ROS generation was reported to upregulate GADD153/CHOP expression and induce ER stress-mediated apoptosis (50,51). In line with the findings of previous studies (48,51), our data showed that ROS-induced ER stress signaling was involved in AITC-induced caspase-3-dependent apoptosis in HT-29 cells.…”

Effect of Different Surface Treatments on Titanium Dental Implant Micro-Morphology

“…When all the torque is concentrated on a smaller contact area versus the entire implant surface, a higher localized stress will result therefrom, which, in turn, can facilitate titanium release in a peri-implant bone [ 46 ]. Wear debris have been assumed to be one of the major factors responsible for aseptic implant loosening [ 47 ]. The real effects of metal and surface contaminant release in the osseointegration process are not yet fully understood, even though it is reported as a possible disturbing factor for bone remodeling balance and severe inflammatory and allergic reactions [ 48 , 49 , 50 , 51 , 52 , 53 ].…”

Carboxymethyl chitosan reduces inflammation and promotes osteogenesis in a rabbit knee replacement model

“…Finally, multiple studies have proven that chitosan and its derivatives have various antioxidant properties [ 28 ]. Yang et al placed wear particles obtained from the interface membrane around a patient’s sterile loosening prosthesis into the primary osteoblasts of rabbits and found that the increased production of reactive oxygen species can induce osteoblast apoptosis [ 29 ]. The specific mechanism is that active oxygen mediates osteoblast apoptosis through the mitochondrial apoptotic protease-dependent pathway and the endoplasmic reticulum stress pathway, and this apoptosis can be attenuated by antioxidant antagonistic effects.…”