Department of Endodontics, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, China.
Protein Cell. 2013 Aug;4(8):620-7. doi: 10.1007/s13238-013-3030-0. Epub 2013 Jul 8.
The differentiation of periodontal ligament (PDL) progenitor cells is important for maintaining the homeostasis of PDL tissue and alveolar bone. Vitamin C (VC), a water-soluble nutrient that cannot be biosynthesized by humans, is vital for mesenchymal stem cells differentiation and plays an important role in bone remodeling. Therefore, the objective of this study was to determine the function and mechanism of VC in PDL progenitor cells osteogenic differentiation at the molecular level. We demonstrated that VC could induce the osteogenic differentiation and maturation of PDL progenitor cell without other osteogenic agents. During the process, VC preferentially activated ERK1/2 but did not affect JNK or p38. Co-treatment with ERK inhibitor effectively decreased the Vitamin C-induced expression of Runx2. ERK inhibitor also abrogated Vitamin C-induced the minimized nodules formation. PELP1, a nuclear receptor co-regulator, was up-regulated under VC treatment. PELP1 knockdown inhibited ERK phosphorylation. The overexpression of PELP1 had a positive relationship with Runx2 expression. Taken together, we could make a conclude that VC induces the osteogenic differentiation of PDL progenitor cells via PELP1-ERK axis. Our finding implies that VC may have a potential in the regeneration medicine and application to periodontitis treatment.
牙周膜（PDL）祖细胞的分化对于维持 PDL 组织和牙槽骨的内稳态至关重要。维生素 C（VC）是一种不能被人体生物合成的水溶性营养素，对间充质干细胞的分化至关重要，并在骨重塑中发挥重要作用。因此，本研究旨在从分子水平上确定 VC 在 PDL 祖细胞成骨分化中的作用和机制。我们证明 VC 可以在没有其他成骨剂的情况下诱导 PDL 祖细胞的成骨分化和成熟。在此过程中，VC 优先激活 ERK1/2，但不影响 JNK 或 p38。ERK 抑制剂的共同处理可有效降低 VC 诱导的 Runx2 表达。ERK 抑制剂还消除了 VC 诱导的最小结节形成。核受体共调节剂 PELP1 在 VC 处理下上调。PELP1 敲低抑制 ERK 磷酸化。PELP1 的过表达与 Runx2 表达呈正相关。综上所述，我们可以得出结论，VC 通过 PELP1-ERK 轴诱导 PDL 祖细胞的成骨分化。我们的发现表明 VC 可能在再生医学和牙周炎治疗的应用中具有潜力。
