Department of Endodontology and Operative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka, Japan.
Cell Tissue Res. 2013 May;352(2):249-63. doi: 10.1007/s00441-012-1543-0. Epub 2013 Jan 17.
Basic fibroblast growth factor (bFGF) is a cytokine that promotes the regeneration of the periodontium, the specialized tissues supporting the teeth. bFGF, does not, however, induce the synthesis of smooth muscle actin alpha 2 (ACTA2), type I collagen (COL1), or COL3, which are principal molecules in periodontal ligament (PDL) tissue, a component of the periodontium. We have suggested the feasibility of using transforming growth factor-β1 (TGFβ1) to induce fibroblastic differentiation of PDL stem/progenitor cells (PDLSCs). Here, we investigated the effect of the subsequent application of TGFβ1 after bFGF (bFGF/TGFβ1) on the differentiation of PDLSCs into fibroblastic cells. We first confirmed the expression of bFGF and TGFβ1 in rat PDL tissue and primary human PDL cells. Receptors for both bFGF and TGFβ1 were expressed in the human PDLSC lines 1-11 and 1-17. Exposure to bFGF for 2 days promoted vascular endothelial growth factor gene and protein expression in both cell lines and down-regulated the expression of ACTA2, COL1, and COL3 mRNA in both cell lines and the gene fibrillin 1 (FBN1) in cell line 1-11 alone. Furthermore, bFGF stimulated cell proliferation of these cell lines and significantly increased the number of cells in phase G2/M in the cell lines. Exposure to TGFβ1 for 2 days induced gene expression of ACTA2 and COL1 in both cell lines and FBN1 in cell line 1-11 alone. BFGF/TGFβ1 treatment significantly up-regulated ACTA2, COL1, and FBN1 expression as compared with the group treated with bFGF alone or the untreated control. This method might thus be useful for accelerating the generation and regeneration of functional periodontium.
碱性成纤维细胞生长因子（bFGF）是一种细胞因子，可促进牙周组织的再生，牙周组织是支持牙齿的特殊组织。然而，bFGF 不会诱导平滑肌肌动蛋白 alpha 2（ACTA2）、I 型胶原（COL1）或 COL3 的合成，这些是牙周韧带（PDL）组织的主要分子，是牙周组织的组成部分。我们已经提出使用转化生长因子-β1（TGFβ1）诱导牙周干细胞/祖细胞（PDLSCs）成纤维细胞分化的可行性。在这里，我们研究了 bFGF（bFGF/TGFβ1）后 TGFβ1 随后应用对 PDLSCs 分化为成纤维细胞的影响。我们首先证实了 bFGF 和 TGFβ1 在大鼠牙周组织和原代人牙周细胞中的表达。bFGF 和 TGFβ1 的受体均在人 PDLSC 系 1-11 和 1-17 中表达。暴露于 bFGF 2 天可促进两种细胞系中血管内皮生长因子基因和蛋白的表达，并下调两种细胞系中 ACTA2、COL1 和 COL3 mRNA 的表达，以及细胞系 1-11 中纤维连接蛋白 1（FBN1）的表达。此外，bFGF 刺激这些细胞系的细胞增殖，并显著增加细胞系中 G2/M 期细胞的数量。暴露于 TGFβ1 2 天可诱导两种细胞系中 ACTA2 和 COL1 的基因表达，以及细胞系 1-11 中 FBN1 的基因表达。与单独用 bFGF 处理或未处理的对照组相比，bFGF/TGFβ1 处理显著上调了 ACTA2、COL1 和 FBN1 的表达。因此，这种方法可能有助于加速功能性牙周组织的生成和再生。
