RESUMO
Ankle osteoarthritis is a relatively understudied condition and the molecular mechanisms involved in its development are not well understood. This investigation aimed to explore the role and underlying molecular mechanisms of Yes-associated protein (YAP) in rat ankle osteoarthritis. The results demonstrated that YAP expression levels were abnormally increased in the ankle osteoarthritis cartilage model. In addition, knockdown of YAP expression was shown to hinder the imbalance in ECM metabolism induced by IL-1ß in chondrocytes, as demonstrated by the regulation of matrix metalloproteinase (MMP)-3, MMP-9, and MMP-13, a disintegrin, metalloprotease with thrombospondin motifs, aggrecan, and collagen II expression. Additional studies revealed that downregulation of YAP expression markedly inhibited the overexpression of ß-catenin stimulated by IL-1ß. Furthermore, inhibition of the Wnt/ß-catenin signaling pathway reversed the ECM metabolism imbalance caused by YAP overexpression in chondrocytes. It is important to note that the YAP-specific inhibitor verteporfin (VP) significantly delayed the progression of ankle osteoarthritis. In conclusion, the findings highlighted the crucial role of YAP as a regulator in modulating the progression of ankle osteoarthritis via the Wnt/ß-catenin signaling pathway. These findings suggest that pharmacological inhibition of YAP can be an effective and critical therapeutic target for alleviating ankle osteoarthritis.
RESUMO
BACKGROUND: Garden I femoral neck fractures are nondisplaced femoral neck fractures. Nonoperative treatment and in situ fixation are the preferred treatments. However, the postoperative outcome is not satisfactory and the incidence of complications remains high, which raises doubts about the accuracy of the diagnosis of nondisplaced Garden I fractures. Recently, three-dimensional (3D) reconstruction has been reported as a mature technology for reconstructing the bone structure of patients. We further extended this technique in the measurement of the fracture spatial displacement to verify the accuracy of Garden I femoral neck fractures. METHODS: This was a retrospective study of patients with Garden I femoral neck fractures from January 2013 to December 2018 at our institution, who were included according to specified criteria. A bilateral proximal femur model of each patient was established based on computed tomography (CT) data. The displacement of the deepest portion of the femoral head fovea, the displacement of the center of the femoral head and the rotation of the femoral head were measured in the bilateral model. RESULTS: A total of 102 patients diagnosed with Garden I fractures were included in this study. The cohort included 32 men and 70 women, with an average age of 55.88 ± 15.32 years. In these patients, the average displacement of the deepest portion of the femoral head fovea was 16.43 ± 7.69 mm. The minimum and maximum displacement was 3.58 and 44.32 mm, respectively. The average displacement of the center of the femoral head was 10.39 ± 5.47 mm and ranged from 2.16 to 34.42 mm. The rotational angle was 23.81 ± 10.15 ° and ranged from 3.71 ° to 61.19 °. CONCLUSIONS: Garden I fractures have large spatial displacement and cannot be considered incomplete or nondisplaced fractures. Therefore, we suggest that anatomical reduction should be considered during treatment.
