Laboratory of Oral Cell Biology, School of Dental Medicine, University of Bern, Bern, Switzerland.
Department of Periodontology, School of Dental Medicine, University of Bern, Bern, Switzerland.
J Periodontal Res. 2019 Feb;54(1):33-45. doi: 10.1111/jre.12602. Epub 2018 Sep 27.
The potential benefit of using hyaluronan (HA) in reconstructive periodontal surgery is still a matter of debate. The aim of the present study was to evaluate the effects of two HA formulations on human oral fibroblasts involved in soft tissue wound healing/regeneration.
Metabolic, proliferative and migratory abilities of primary human palatal and gingival fibroblasts were examined upon HA treatment. To uncover the mechanisms whereby HA influences cellular behavior, wound healing-related gene expression and activation of signaling kinases were analyzed by qRT-PCR and immunoblotting, respectively.
The investigated HA formulations maintained the viability of oral fibroblasts and increased their proliferative and migratory abilities. They enhanced expression of genes encoding type III collagen and transforming growth factor-β3, characteristic of scarless wound healing. The HAs upregulated the expression of genes encoding pro-proliferative, pro-migratory, and pro-inflammatory factors, with only a moderate effect on the latter in gingival fibroblasts. In palatal but not gingival fibroblasts, an indirect effect of HA on the expression of matrix metalloproteinases 2 and 3 was detected, potentially exerted through induction of pro-inflammatory cytokines. Finally, our data pointed on Akt, Erk1/2 and p38 as the signaling molecules whereby the HAs exert their effects on oral fibroblasts.
Both investigated HA formulations are biocompatible and enhance the proliferative, migratory and wound healing properties of cell types involved in soft tissue wound healing following regenerative periodontal surgery. Our data further suggest that in gingival tissues, the HAs are not likely to impair the healing process by prolonging inflammation or causing excessive MMP expression at the repair site.
透明质酸(HA)在牙周组织再生术中的潜在益处仍存在争议。本研究旨在评估两种 HA 制剂对参与软组织创伤愈合/再生的人口腔成纤维细胞的影响。
HA 处理后,检测原代人腭部和牙龈成纤维细胞的代谢、增殖和迁移能力。通过 qRT-PCR 和免疫印迹分别分析 HA 影响细胞行为的机制以及与伤口愈合相关的基因表达和信号激酶的激活。
所研究的 HA 制剂维持了口腔成纤维细胞的活力,并增强了其增殖和迁移能力。它们增加了编码 III 型胶原和转化生长因子-β3 的基因的表达,这是无瘢痕愈合的特征。HA 上调了编码促增殖、促迁移和促炎因子的基因表达,而在牙龈成纤维细胞中,对后者的影响仅为中度。在腭部而非牙龈成纤维细胞中,检测到 HA 对基质金属蛋白酶 2 和 3 的表达具有间接影响,可能通过诱导促炎细胞因子发挥作用。最后,我们的数据表明 Akt、Erk1/2 和 p38 是 HA 对口腔成纤维细胞发挥作用的信号分子。
两种研究中的 HA 制剂均具有生物相容性,并增强了参与再生性牙周手术后软组织伤口愈合的细胞类型的增殖、迁移和伤口愈合特性。我们的数据进一步表明,在牙龈组织中,HA 不太可能通过延长炎症或在修复部位引起过度的 MMP 表达来损害愈合过程。