Department of Rheumatology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
IUBMB Life. 2019 Jul;71(7):854-862. doi: 10.1002/iub.2016. Epub 2019 Feb 6.
Preptin, an oligopeptide secreted by pancreatic β-cell, plays a significant role in glycometabolism and bone metabolism. Preptin strengthens proliferation and differentiation of osteoblasts, but the mechanism is unclear. Here, we explored the role of the Wnt/β-catenin signaling pathway which is well known to affect bone development and remodelling in the function of preptin. We found that preptin promoted the cell proliferative activity and osteoblastic differentiation in osteoblast-like MC3T3-E1 cells in a dose-independent manner, as evidenced by elevation in osteogenic genes, alkaline phosphatase activity and alizarin red staining in a dose-independent manner. Additionally, our findings demonstrated that the β-catenin expression level and runt-related transcription factor 2, which is the key downstream target of this pathway, were increased. The Wnt/β-catenin signalling pathway antagonist DKK1 abrogated the proliferative effect and differentiation function of preptin in MC3T3-E1 cells. These data indicated that preptin may be a potential therapeutic target for the treatment of osteoporosis and that osteogenic impact of preptin in MC3T3-E1 cells might be mediated by the Wnt/β-catenin signalling pathway. © 2019 IUBMB Life, 9999(9999):1-9, 2019.
Preptin 是一种由胰腺β细胞分泌的低聚肽，在糖代谢和骨代谢中发挥重要作用。Preptin 可增强成骨细胞的增殖和分化，但具体机制尚不清楚。本研究探讨了 Wnt/β-catenin 信号通路在 Preptin 功能中的作用，该通路已知可影响骨的发育和重塑。我们发现 Preptin 可独立于剂量依赖性地促进成骨样 MC3T3-E1 细胞的细胞增殖活性和成骨分化，其证据为成骨基因、碱性磷酸酶活性和茜素红染色均独立于剂量依赖性地升高。此外，我们的研究结果表明β-catenin 表达水平和 runt 相关转录因子 2（该通路的关键下游靶标）增加。Wnt/β-catenin 信号通路拮抗剂 DKK1 可阻断 Preptin 在 MC3T3-E1 细胞中的增殖作用和分化功能。这些数据表明 Preptin 可能是治疗骨质疏松症的潜在治疗靶点，并且 Preptin 在 MC3T3-E1 细胞中的成骨作用可能是通过 Wnt/β-catenin 信号通路介导的。© 2019 IUBMB Life, 9999(9999):1-9, 2019.
