Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, 130-701, Korea.
Mol Cells. 2010 Nov;30(5):449-54. doi: 10.1007/s10059-010-0139-3. Epub 2010 Sep 10.
Wnt/β-catenin signaling has been known to influence bone formation and homeostasis. In this study, we investigated the canonical Wnt signaling regulation of osteogenic differentiation from periodontal ligament (PDL) fibroblasts. Stimulating PDL fibroblasts with lithium chloride (LiCl), a canonical Wnt activator, significantly increased mineralized nodule and alkaline phosphatase (ALP) activity in a time- and dose-dependent manner. LiCl up-regulated protein expression of osteogenic transcription factors, including the runt-related gene 2, Msx2, and Osterix 2, in the PDL fibroblasts. Treatment of these cells with LiCl also increased the mRNA levels of ALP, FosB, and Fra1 in a dose-dependent manner. Blockage of canonical Wnt signaling by treating the cells with DKK1 inhibited Wnt1-stimulated mRNA expression of these osteogenic factors. Furthermore, pretreatment with DKK1 reduced the ALP activity and matrix mineralization stimulated by Wnt1. Collectively, these results suggest that canonical Wnt signaling leads to the differentiation of PDL fibroblasts into osteogenic lineage with the attendant stimulation of osteogenic transcription factors.
Wnt/β-连环蛋白信号通路已被证实能够影响骨形成和稳态。在这项研究中，我们研究了经典 Wnt 信号通路对牙周膜（PDL）成纤维细胞成骨分化的调控作用。用氯化锂（LiCl）刺激 PDL 成纤维细胞，一种经典的 Wnt 激活剂，可显著增加矿化结节和碱性磷酸酶（ALP）活性，呈时间和剂量依赖性。LiCl 上调了 PDL 成纤维细胞中成骨转录因子的蛋白表达水平，包括 runt 相关基因 2、Msx2 和 Osterix 2。LiCl 处理这些细胞还可呈剂量依赖性地增加 ALP、FosB 和 Fra1 的 mRNA 水平。用 DKK1 阻断经典 Wnt 信号通路可抑制 Wnt1 刺激的这些成骨因子的 mRNA 表达。此外，DKK1 的预处理可降低 Wnt1 刺激的 ALP 活性和基质矿化。综上所述，这些结果表明，经典 Wnt 信号通路可诱导 PDL 成纤维细胞向成骨谱系分化，并伴随成骨转录因子的刺激。
