The secretome of human dental pulp stem cells protects myoblasts from hypoxia‑induced injury via the Wnt/β‑catenin pathway

人类牙髓干细胞分泌组通过 Wnt/β-catenin 通路保护成肌细胞免受缺氧损伤

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作者:Weihua Zhang, Liming Yu, Xinxin Han, Jie Pan, Jiajia Deng, Luying Zhu, Yun Lu, Wei Huang, Shangfeng Liu, Qiang Li, Yuehua Liu

Abstract

Human dental pulp stem cells (hDPSCs) present several advantages, including their ability to be non‑invasively harvested without ethical concern. The secretome of hDPSCs can promote the functional recovery of various tissue injuries. However, the protective effects on hypoxia‑induced skeletal muscle injury remain to be explored. The present study demonstrated that C2C12 myoblast coculture with hDPSCs attenuated CoCl2‑induced hypoxic injury compared with C2C12 alone. The hDPSC secretome increased cell viability and differentiation and decreased G2/M cell cycle arrest under hypoxic conditions. These results were further verified using hDPSC‑conditioned medium (hDPSC‑CM). The present data revealed that the protective effects of hDPSC‑CM depend on the concentration ratio of the CM. In terms of the underlying molecular mechanism, hDPSC‑CM activated the Wnt/β‑catenin pathway, which increased the protein levels of Wnt1, phosphorylated‑glycogen synthase kinase‑3β and β‑catenin and the mRNA levels of Wnt target genes. By contrast, an inhibitor (XAV939) of Wnt/β‑catenin diminished the protective effects of hDPSC‑CM. Taken together, the findings of the present study demonstrated that the hDPSC secretome alleviated the hypoxia‑induced myoblast injury potentially through regulating the Wnt/β‑catenin pathway. These findings may provide new insight into a therapeutic alternative using the hDPSC secretome in skeletal muscle hypoxia‑related diseases.

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