Abstract
Wear particle-induced periprosthetic osteolysis is mainly responsible for joint replacement failure and revision surgery. Curculigoside is reported to have bone-protective potential, but whether curculigoside attenuates wear particle-induced osteolysis remains unclear. In this study, titanium particles (Ti) were used to stimulate osteoblastic MC3T3-E1 cells in the presence or absence of curculigoside, to determine their effect on osteoblast differentiation. Rat osteoclastic bone marrow stromal cells (BMSCs) were cocultured with Ti in the presence or absence of curculigoside, to evaluate its effect on osteoclast formation in vitro. Ti was also used to stimulate mouse calvaria to induce an osteolysis model, and curculigoside was administrated to evaluate its effect in the osteolysis model by micro-CT imaging and histopathological analyses. As the results indicated, in MC3T3-E1 cells, curculigoside treatment attenuated the Ti-induced inhibition on cell differentiation and apoptosis, increased alkaline phosphatase activity (ALP) and cell mineralization, and inhibited TNF-α, IL-1β, and IL-6 production and ROS generation. In BMSCs, curculigoside treatment suppressed the Ti-induced cell formation and suppressed the TNF-α, IL-1β, and IL-6 production and F-actin ring formation. In vivo, curculigoside attenuated Ti-induced bone loss and histological damage in murine calvaria. Curculigoside treatment also reversed the RANK/RANKL/OPG and NF-κB signaling pathways, by suppressing the RANKL and NF-κB expression, while activating the OPG expression. Our study demonstrated that curculigoside treatment was able to attenuate wear particle-induced periprosthetic osteolysis in in vivo and in vitro experiments, promoted osteoblastic MC3T3-E1 cell differentiation, and inhibited osteoclast BMSC formation. It suggests that curculigoside may be a potential pharmaceutical agent for wear particle-stimulated osteolysis therapy.
Highlights
It is no doubt that total joint arthroplasty (TJA) is a landmark of orthopedic surgery in the 20th century, with the notable advantages of joint pain relief and joint function restoration in patients with bone and articular maladies [1]
After osteoblast MC3T3-E1 cells were intervened with titanium particles (Ti) and treated with curculigoside at different concentrations (25, 50, and 100 μg/ml) for 24 h, 48 h, and 72 h, cell viability was detected by the CCK-8 assay
flow cytometry (FCM) results in Figures 1(b) and 1(d) showed that after Ti intervention, the MC3T3-E1 cell apoptosis rate was significantly increased compared to the Con group, while in curculigoside-treated groups at different concentrations, cell apoptosis was decreased
Summary
It is no doubt that total joint arthroplasty (TJA) is a landmark of orthopedic surgery in the 20th century, with the notable advantages of joint pain relief and joint function restoration in patients with bone and articular maladies [1]. A followup study of more than 15 years reported that approximately 82% of total knee replacements (TKRs) last 25 years and. 70% of unicondylar knee replacements (UKRs) last 25 years; the 25-year pooled survival rate of hip replacements and joint replacement was 77.6% and 57.9%, respectively, indicating generally excellent outcomes of TJA [2, 3]. All TJA will eventually fail because of the gradually emerged issues, such as infection, fracture, or loosening and wear. These factors are the most prevalent reasons for TJA revision. Journal of Immunology Research loosening (38%) is higher than the sum of deep infection and periprosthetic fractures, and most of the aseptic loosening is caused by particle wear and thereby induced osteolysis [4, 5]. Osteolysis has become a key challenge restricting the life of artificial joint and is the main cause of TJA renovation
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