YY1/miR-140-5p/Jagged1/Notch axis mediates cartilage progenitor/stem cells fate reprogramming in knee osteoarthritis.

Osteoarthritis is a multifactorial disease characterized by cartilage degeneration, while cartilage progenitor/stem cells (CPCs) are responsible for endogenous cartilage repair. However, the relevant regulatory mechanisms of CPCs fate reprogramming in OA are rarely reported. Recently, we observed fate disorders in OA CPCs and found that microRNA-140-5p (miR-140-5p) protects CPCs from fate changes in OA. This study further mechanistically investigated the upstream regulator and downstream effectors of miR-140-5p in OA CPCs fate reprogramming. As a result, luciferase reporter assay and validation assays revealed that miR-140-5p targets Jagged1 and inhibits Notch signaling in human CPCs, and the loss-/gain-of-function experiments and rescue assays discovered that miR-140-5p improves OA CPCs fate, but this effect can be counteracted by Jagged1. Moreover, increased transcription factor Ying Yang 1 (YY1) was associated with OA progression, and YY1 could disturb CPCs fate via transcriptionally repressing miR-140-5p and enhancing the Jagged1/Notch signaling. Finally, the relevant changes and mechanisms of YY1, miR-140-5p, and Jagged1/Notch signaling in OA CPCs fate reprogramming were validated in rats. Conclusively, this study identified a novel YY1/miR-140-5p/Jagged1/Notch signaling axis that mediates OA CPCs fate reprogramming, wherein YY1 and Jagged1/Notch signaling exhibits an OA-stimulative role, and miR-140-5p plays an OA-protective effect, providing attractive targets for OA therapeutics.

Comparison of the Efficacy and Safety of Aspirin and Rivaroxaban Following Enoxaparin Treatment for Prevention of Venous Thromboembolism after Hip Fracture Surgery.

OBJECTIVE: To compare the efficacy and safety of aspirin with rivaroxaban following treatment with enoxaparin for prevention of venous thromboembolism (VTE) after hip fracture surgery (HFS). METHODS: A total of 390 patients were enrolled in the trial. According to an odd or even number at the end of their registration number, the patients were divided into the aspirin group (n = 198) and the rivaroxaban group (n = 192). All patients were given enoxaparin subcutaneous injection after the operation and returned to the routine dose the next day until postoperative day five. The patients in the aspirin group received an additional 16 days of thromboprophylaxis with 100 mg of aspirin once daily. The rivaroxaban group was assigned to receive an additional 16 days of thromboprophylaxis with 10 mg of oral rivaroxaban once daily. Patients were followed for 90 days regarding VTE and bleeding complications. RESULTS: The incidence of VTE in the aspirin group and rivaroxaban group was 6.6% (13/198) and 5.7% (11/192), respectively (P = 0.83). The rate of major bleeding events occurred in two (1.0%) patients in the aspirin group and in one patient (0.5%) in the rivaroxaban group (P = 1.0). A combination of major bleeding and clinically relevant nonmajor bleeding occurred in five patients (2.5%) in the aspirin group and in six patients (3.1%) in the rivaroxaban group (P = 0.77). During the 90-day follow-up, a pulmonary embolism developed in one patient (0.5%) in the aspirin group and none in the rivaroxaban group (P = 1.0). CONCLUSIONS: Extended prophylaxis for 21 days with aspirin was equivalent to the direct oral anticoagulant rivaroxaban after hip fracture surgery with an initial 5-day postoperative course of enoxaparin. Aspirin may be an effective, safe, convenient, and cheap alternative for extended prophylaxis after hip fracture surgery.