Tumor protein p53-induced nuclear protein 2 modulates osteogenic differentiation of human adipose derived stem/stromal cells by activating Wnt/β-catenin signaling

肿瘤蛋白p53诱导的核蛋白2通过激活Wnt/β-catenin信号通路调节人脂肪来源干/基质细胞的成骨分化

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作者:Shi Dong ,Jie Li ,Xiaonan Zhang

Abstract

Human adipose derived stem/stromal cells (hASCs) are frequently used as seed cells in bone tissue engineering. These cells have good osteogenic properties in various in vivo and in vitro models. Tumor protein p53-induced nuclear protein 2 (TP53INP2) regulates apoptosis, autophagy, and cell differentiation. However, whether TP53INP2 regulates osteogenic differentiation of hASCs has not been sufficiently studied. Herein, we explored this topic using siRNA experiments, osteogenic induction, quantitative real-time PCR (qRT-PCR) and western blot analysis. We found that siRNA decreased mRNA levels of osteoblast-specific genes in TP53INP2 cells. Western blots showed that RUNX2 protein expression decreased in siRNA-TP53INP2 cells at day 3, 7, and 21 after osteogenic induction. The level of β-catenin, LC3 and the LC3-II/LC3-I ratio in siRNA-TP53INP2 cells was decreased at day 3 and 7 after osteogenic induction. Further, treatment with lithium chloride (LiCl), an activator of Wnt signaling pathway, induced partial recovery of protein expression of β-catenin and RUNX2 (osteoblast-specific factor 2) in TP53INP2 knockdown cells. Collectively, these results show that TP53INP2 promotes osteogenic differentiation of hASCs by activating Wnt/β-catenin signaling.

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