Medical University Sofia, Dept. of Medical Chemistry and Biochemistry, 2 Zdrave Str. Sofia, 1431, Bulgaria.
Agrobioinstitute, Agricultural Academy, Dr. Tsankov Blvd 8, 1164 Sofia, Bulgaria.
J Proteomics. 2018 Jul 15;183:14-24. doi: 10.1016/j.jprot.2018.05.004. Epub 2018 May 11.
FGF8 specifies early tooth development by directing the migration of the early tooth founder cells to the site of tooth emergence. To date the effect of the FGF8 in adult dental pulp has not been studied. We have assessed the regenerative potential of FGF8 by evaluating changes in the proteome landscape of dental pulp following short- and long-term exposure to recombinant FGF8 protein. In addition, we carried out qRT PCR analysis to determine extracellular/adhesion gene marker expression and assessed cell proliferation and mineralization in response to FGF8 treatment. 2D and mass spectrometry data showed differential expression of proteins implicated in cytoskeleton/ECM remodeling and migration, cell proliferation and odontogenic differentiation as evidenced by the upregulation of gelsolin, moesin, LMNA, WDR1, PLOD2, COPS5 and downregulation of P4HB. qRT PCR showed downregulation of proteins involved in cell-matrix adhesion such as ADAMTS8, LAMB3 and ANOS1 and increased expression of the angiogenesis marker PECAM1. We have observed that, FGF8 treatment was able to boost dental pulp cell proliferation and to enhance dental pulp mineralization. Collectively, our data suggest that, FGF8 treatment could promote endogenous healing of the dental pulp via recruitment of dental pulp progenitors as well as by promoting their angiogenic and odontogenic differentiation.
Dental pulp cells (DP) have been studied extensively for the purposes of mineralized tissue repair, particularly for the reconstruction of hard and soft tissue maxillofacial defects. Canonical FGF signaling has been implicated throughout multiple stages of tooth development by regulating cell proliferation, differentiation, survival as well as cellular migration. FGF8 expression is indispensible for normal tooth development and particularly for the migration of early tooth progenitors to the sites of tooth emergence. The present study provides proteome and qRT PCR data with regard to the future application and biological relevance of FGF8 in dental regenerative medicine.
Rozaliya Tsikandelova - 0000-0003-0178-3767 Zornitsa Mihaylova - 0000-0003-1748-4489 Sébastien Planchon - 0000-0002-0455-0574 Nikolay Ishkitiev - 0000-0002-4351-5579.
FGF8 通过指导早期牙祖细胞向牙齿萌出部位迁移，指定早期牙齿发育。迄今为止，尚未研究 FGF8 在成人牙髓中的作用。我们通过评估短时间和长时间暴露于重组 FGF8 蛋白后牙髓蛋白质组景观的变化，评估了 FGF8 的再生潜力。此外，我们进行了 qRT-PCR 分析，以确定细胞外/粘附基因标记的表达，并评估了对 FGF8 治疗的细胞增殖和矿化的反应。2D 和质谱数据分析显示，与细胞骨架/ECM 重塑和迁移、细胞增殖和牙源性分化有关的蛋白质表达差异，这表现在凝胶蛋白、膜突蛋白、LMNA、WDR1、PLOD2、COPS5 的上调和 P4HB 的下调。qRT-PCR 显示细胞-基质粘附相关蛋白如 ADAMTS8、LAMB3 和 ANOS1 的下调和血管生成标记物 PECAM1 的表达增加。我们观察到，FGF8 处理能够促进牙髓细胞的增殖，并增强牙髓的矿化。总的来说，我们的数据表明，FGF8 处理可以通过招募牙髓祖细胞并促进其血管生成和牙源性分化来促进牙髓的内源性愈合。
牙髓细胞 (DP) 已被广泛研究用于矿化组织修复，特别是用于重建硬组织和软组织颌面缺损。经典的 FGF 信号转导通过调节细胞增殖、分化、存活以及细胞迁移，参与了牙齿发育的多个阶段。FGF8 的表达对于正常的牙齿发育，特别是早期牙齿祖细胞向牙齿萌出部位的迁移是必不可少的。本研究提供了有关 FGF8 在牙髓再生医学中的未来应用和生物学相关性的蛋白质组和 qRT-PCR 数据。
作者 ORCID：Rozaliya Tsikandelova-0000-0003-0178-3767 Zornitsa Mihaylova-0000-0003-1748-4489 Sébastien Planchon-0000-0002-0455-0574 Nikolay Ishkitiev-0000-0002-4351-5579。
