The proinflammatory cytokine interleukin-1 β (IL-1β)-mediated cellular senescence in chondrocytes is involved in the development and pathological progression of osteoarthritis (OA). Feprazone, a nonsteroidal anti-inflammatory drug (NSAID) and a cyclooxygenase (COX) inhibitor, is widely used in clinics. This study aims to investigate whether Feprazone has a protective effect against IL-1β-induced cellular senescence in human chondrocytes. In this study, C-28/I2 chondrocytes were stimulated with IL-1β (10 ng/mL) in the presence or absence of Feprazone (10 and 20 μM). Cellular senescence was assessed using senescence-associated β-galactosidase (SA-β-Gal) staining. The cell cycle was examined using flow cytometry. Gene and protein expressions were determined with real-time polymerase chain reaction (PCR) and western blot analysis. We found that treatment with Feprazone ameliorated IL-1β-induced increase in cellular senescence. Feprazone increased telomerase activity and prevented cell cycle arrest in the G0/G1 phase. We also found that Feprazone reduced the expressions of plasminogen activator inhibitor-1 (PAI-1) and p21, two important regulators of cellular senescence. Additionally, treatment with Feprazone reduced the expressions of matrix metalloprotein (MMP-13) and a disintegrin-like and metalloproteinase with thrombospondin type-1 motif-5 (ADAMTS-5). Interestingly, Feprazone prevented the activation of nuclear factor kappa-B (NF-κB) by preventing nuclear translocation of NF-κB p65 and the luciferase activity of the NF-κB promoter. The results also show that Feprazone increased nuclear levels of nuclear factor erythroid 2-related factor-2 (Nrf2) and reduced the production of reactive oxygen species (ROS). Importantly, silencing of Nrf2 abolished the protective effects of Feprazone against IL-1β-induced NF-κB activation and cellular senescence. These findings shed light on the potential use of Feprazone in the treatment of OA based on a novel mechanism.

Objective. This study is aimed at studying the effect of zoledronate (ZOL) on the differentiation of osteoclast precursor RAW264.7 cells induced by titanium (Ti) particles and explores the possibility of preventing and treating periprosthetic osteoporosis using ZOL. Methods. RAW264.7 cells were cultured in vitro. Ti particles were prepared. The cell proliferation curve of RAW264.7 cells was plotted using the MTT assay to find the best concentration of ZOL for intervention. The cells were divided into three groups: control, Ti particles, and Ti particles+ZOL. The cell morphology was observed using tartaric acid–resistant acid phosphatase (TRAP) staining, and the activity of TRAP in cell supernatant was determined using the biochemical method. The number of bone resorption lacunae was detected using toluidine blue staining. The mRNA expression of RANK, NFATcl, CAII, and MMP-9 was detected using real-time polymerase chain reaction. The protein expression of RANK, NFATcl, and MMP-9 was detected using Western blot analysis. Results. Ti particles stimulated the differentiation of RAW264.7 cells into osteoclasts. They also increased the activity of TRAP, number of bone resorption lacunae, and mRNA and protein expression of RANK, NFATcl, and MMP-9. However, ZOL could suppress the effect of TI particles on the osteoclast differentiation of RAW264.7 cells. Conclusions. ZOL could effectively inhibit the differentiation of RAW264.7 cells into osteoclasts induced by Ti particles, decrease the activity of TRAP, reduce the number of bone resorption lacunae, and decrease the mRNA and protein expression of RANK, NFATcl, and MMP-9. Hence, it may be a promising candidate for preventing and treating periprosthetic osteoporosis after the artificial joint operation.

Background The purpose of this study was to compare the clinical and radiological outcomes of displaced intra-articular calcaneus fractures (DIACFs) treated with small locking plates alone versus small locking plates combined with screws. Methods Retrospective analysis of 120 patients with intra-articular fractures seen from May 2018 to June 2020, all of whom were surgically repositioned using sinus tarsal approach.60 cases received a small locking plate combined with screws fixation (observation group) and 60 cases received a small locking plate fixation alone (control group).Demographic variables were recorded and compared Gissane angle, Bohler's angle, calcaneal varus, and joint line parallel angle at 3 days and 2 years postoperative follow-up.The American Orthopaedic Foot and Ankle Society (AOFAS) Ankle and Hindfoot Score and VAS were applied to assess postoperative foot function, and complications were also compared. Results Compared with the control group, the joint line parallel angle and calcaneal varus in the observation group had lower displacement changes from the postoperative period to the 2-year follow-up,they are 0.07 (0.15) degrees vs 0.47 (0.59) degrees(P < 0.001), 0.19 (0.35) degrees vs 1.18 (0.67) degrees(P < 0.001).There was no significant difference in Gissane angle and Bohler's angle between the observation group and the control group at the preoperative, 3-year and 2-year follow-up (P > 0.05).The final AOFAS score, VAS score and complications were not significantly different between the two groups (P > 0.05). Conclusion When STA is used to treat DIACFs, fixation with a small locking plate combined with screws appears to provide better posterior articular surface stability and better maintenance of calcaneal axial stability than fixation with a small locking plate alone,the two techniques had similar functional outcomes and complications after surgery.

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