Lipopolysaccharide can modify differentiation and immunomodulatory potential of periodontal ligament stem cells via ERK1,2 signaling
Lipopolysaccharide can modify differentiation and immunomodulatory potential of periodontal ligament stem cells via ERK1,2 signaling
复制标题
DOI：
10.1002/jcp.25904
复制
发表时间：
2018-01-01
影响因子：
5.6
通讯作者：
Bugarski, Diana
中科院分区：
文献类型：
--
作者：
Kukolj, Tamara;Trivanovic, Drenka;Bugarski, Diana
脂多糖（LPS）是口腔微环境中的一种相关有害因子，对作为再生过程载体的细胞有害。本研究旨在探讨脂多糖（大肠杆菌）对人牙周膜干细胞（PDLSC）功能和相关信号通路的影响。我们证明LPS不影响PDLSC的免疫表型、增殖、活力和细胞周期。然而，LPS通过下调Runx 2、ALP和Ocn mRNA表达来修饰PDLSC的谱系定型，从而抑制骨生成，同时通过上调Sox 9和PPAR mRNA表达来刺激软骨生成和脂肪生成。LPS促进PDLSC的成肌纤维细胞样表型，因为它显著增强PDLSC收缩性，以及TGF-β、纤连蛋白（FN）、α-SMA和NG 2的蛋白质和/或基因表达。LPS还增加PDLSC中抗炎考克斯-2和促炎IL-6分子的蛋白和基因表达水平。在LPS处理的PDLSC存在下，外周血单核细胞（MNC）跨内皮迁移的抑制伴随着MNC内CD 29表达的降低。LPS处理后，PDLSCs对丝裂原刺激的CD 4（+）淋巴细胞增殖的抑制作用及CD 4（+）CD 25（high）/CD 4（+）CD 25（low）比值均无明显改变。LPS处理的PDLSC没有改变MNC中CD 34（+）和CD 45（+）细胞的频率，但降低了CD 33（+）和CD 14（+）髓样细胞的频率。此外，LPS处理减弱了PDLSC对MNC CFC活性的刺激作用，主要是CFU-GM数量。结果表明，LPS激活的ERK 1，2至少部分参与了观察到的PDLSC分化能力，肌纤维母细胞属性的收购，和它们的免疫调节功能的变化的影响。
Lipopolysaccharide (LPS) is a pertinent deleterious factor in oral microenvironment for cells which are carriers of regenerative processes. The aim of this study was to investigate the emerging in vitro effects of LPS (Escherichia coli) on human periodontal ligament stem cell (PDLSC) functions and associated signaling pathways. We demonstrated that LPS did not affect immunophenotype, proliferation, viability, and cell cycle of PDLSCs. However, LPS modified lineage commitment of PDLSCs inhibiting osteogenesis by downregulating Runx2, ALP, and Ocn mRNA expression, while stimulating chondrogenesis and adipogenesis by upregulating Sox9 and PPAR mRNA expression. LPS promoted myofibroblast-like phenotype of PDLSCs, since it significantly enhanced PDLSC contractility, as well as protein and/or gene expression of TGF-beta, fibronectin (FN), alpha-SMA, and NG2. LPS also increased protein and gene expression levels of anti-inflammatory COX-2 and pro-inflammatory IL-6 molecules in PDLSCs. Inhibition of peripheral blood mononuclear cells (MNCs) transendothelial migration in presence of LPS-treated PDLSCs was accompanied by the reduction of CD29 expression within MNCs. However, LPS treatment did not change the inhibitory effect of PDLSCs on mitogen-stimulated proliferation of CD4(+) and the ratio of CD4(+)CD25(high)/CD4(+)CD25(low) lymphocytes. LPS-treated PDLSCs did not change the frequency of CD34(+) and CD45(+) cells, but decreased the frequency of CD33(+) and CD14(+) myeloid cells within MNCs. Moreover, LPS treatment attenuated the stimulatory effect of PDLSCs on CFC activity of MNCs, predominantly the CFU-GM number. The results indicated that LPS-activated ERK1,2 was at least partly involved in the observed effects on PDLSC differentiation capacity, acquisition of myofibroblastic attributes, and changes of their immunomodulatory features.