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Mesenchymal stem cells (MSCs) have been shown to be involved in bone injury repair. Programmed cell death 4 (PDCD4) is not only a tumor suppressor gene but also plays roles in the regulation of MSC function. The aim of the study was to uncover PDCD4 potential regulatory roles and mechanisms in the osteogenic differentiation and bone defect repair of MSCs. shRNA technique was used to knock down PDCD4 expression in umbilical cord-derived mesenchymal stem cells (shPDCD4-UCMSCs). Their phenotype was characterized by flow cytometry and the differentiation potential was verified. We found that PDCD4 knockdown did not affect the surface molecule expression of UCMSCs, but significantly enhanced their osteogenic differentiation and osteogenesis-related molecule expression. Mechanistically, glycogen synthase kinase-3β (GSK-3β) phosphorylation and β-catenin expression were significantly increased in shPDCD4-UCMSCs during the osteogenic differentiation process. The β-catenin inhibitor PNU-74654 reversed shPDCD4-increased osteogenesis and osteogenesis-related molecule expression. The results of animal experiments showed that shPDCD4-UCMSCs markedly improved the defect healing in rabbits. Our findings suggest that PDCD4 acts as a negative regulator of MSC osteogenic differentiation through GSK-3β/β-catenin pathway. Targeting PDCD4 may be a way to improve MSC-mediated therapeutic effects on bone injury. [ABSTRACT FROM AUTHOR]

Bovine tuberculosis (bTB) is a major chronic bacterial disease in cattle and is the major economic and animal welfare issue in the world. Although the economic costs and public health safety risks associated with the disease are considerable, the overall epidemiology of the Chinese yak (Bos grunniens) bTB is unclear. To fully reveal the basic prevalence of yak bTB in different regions of China, we searched five databases including PubMed, Science Direct, CNKI (China National Knowledge Infrastructure), Wanfang and Chongqing VIP. Based on the incidence and prevalence of yak tuberculosis in China from 1982 to 2020, a meta-analysis of yak bTB in China was established for the first time. By formulating the search formula, 97 studies were searched in five databases. According to the established exclusion criteria and excluded comments and repeated and irrelevance research, we finally selected 19 cross-sectional studies, which showed the prevalence of bTB in Chinese yaks. Random-effect meta-regression model analysis showed that the estimated prevalence of 122,729 yaks in China was 1.0 (95% confidence interval [CI]: 0.0-1.0). The regional prevalence varies greatly, northwest China prevalence rate 0. 39% (95% CI: 0.2-0. 64) and southwest China prevalence rate 2.59% (95% CI: 1.94-3.34); in terms of province level, the prevalence was highest in Tibet 2.59% (95% CI: 1.94-3.34), followed by Xinjiang 2.36% (95% CI: 0.86-4.58), and Shanxi has the lowest 0.00% (95% CI: 0.00-0.98). This systematic review and meta-analysis identified the estimated prevalence of bTB in Chinese yaks and estimated the underlying factors associated with bTB, including geographic location, sampling year, age, and TB detection method. Provide evidence to plan corresponding disease control strategies for policymakers and to assess future economic risks accurately. [ABSTRACT FROM AUTHOR]