NEAT1/miR-146a-3p/TrkB/ShcB axis regulates the development and function of chondrocyte.
The current study aimed to explored the regulatory effect of Tropomyosin-related kinases B (TrkB) in the development and function of chondrocyte. Correlation between clinicopathological characteristics and osteoarthritis (OA) were analyzed. The expressions of TrkA, brain-derived neurotrophic factor (BDNF), TrkB, Src homolog and collagen homolog B (ShcB), and ShcC in OA cartilage tissue and IL-1β-stimulated chondrocytes from normal cartilage were determined by Western blot/qRT-PCR. After manipulating the expressions of TrkA, shTrkB, ShcB, miR-146a-3p and nuclear paraspeckle assembly transcript 1 (NEAT1), the differentiation-related molecules, and apoptosis-related molecules were examined by Western blot/qRT-PCR, and migration, invasion, proliferation, tube formation, and apoptosis rate in IL-1β-stimulated chondrocyte were examined by scratch, Transwell, colony formation, and tube formation, and flow cytometry assays, respectively. Bioinformatics, dual-luciferase and Spearman were used to analyze the binding and correlation of target genes. The findings showed that OA was related to body mass Index (BMI). The expressions of TrkA, TrkB and ShcB and NEAT1 were up-regulated in OA and IL-1β-stimulated chondrocytes, while miR-146a-3p was donwnregulated and was negatively correlated with TrkB or NEAT1. NEAT1 competed with TrkB in chondrocytes for miR-146a-3p binding. ShTrkB reversed the decrease in expressions of differentiation-related molecules, migration, invasion and proliferation, and the increase in ShcB expression and tube formation, of IL-1β-stimulated chondrocytes. Overexpressed ShcB reversed effect of shTrkB on the functions of IL-1β-stimulated chondrocytes. MiR-146a-3p inhibitor reversed effects of shTrkB on the function and apoptosis-related molecules on IL-1β-stimulated chondrocytes, while NEAT1 reversed role of miR-146a-3p. This paper demonstrated that NEAT1/miR-146a-3p/TrkB/ShcB axis regulates the development and function of chondrocyte.
['Ning|Fanyou|F|', 'Zhu|Shaobo|S|', 'Gao|Hui|H|', 'Deng|Yu|Y|']
miR-146a-3p chondrocyte tropomyosin-related kinases B Osteoarthritis nuclear paraspeckle assembly transcript 1