Prolonged exposure to bacterial toxins downregulated expression of toll-like receptors in mesenchymal stromal cell-derived osteoprogenitors.
Prolonged exposure to bacterial toxins downregulated expression of toll-like receptors in mesenchymal stromal cell-derived osteoprogenitors.
复制标题
在间充质基质细胞衍生的骨基因生成剂中，长时间暴露于细菌毒素下调Toll样受体的表达。
DOI：
10.1186/1471-2121-9-52
复制
发表时间：
2008-09-18
期刊：
影响因子：
--
通讯作者：
Chan, Godfrey Chi Fung
中科院分区：
文献类型：
--
作者：
Mo, Irene Fung Ying;Yip, Kevin Hak Kong;Chan, Wing Keung;Law, Helen Ka Wai;Lau, Yu Lung;Chan, Godfrey Chi Fung
人间充质干细胞（mesenchymal stromal cells，MSCs）是一种具有潜在治疗价值的多能细胞。骨髓间充质干细胞具有成骨能力，在临床上可用于促进牙种植体的骨整合或骨缺损的矫形修复。然而，伤口感染或口腔微生物菌群是否会干扰人MSC的生长和成骨分化仍然未知。本研究调查了MSC的增殖和成骨分化是否会受到人类环境中常见的强效革兰氏阳性和革兰氏阴性衍生细菌毒素的影响。我们选择大肠杆菌的脂多糖（LPS）和化脓性链球菌的脂磷壁酸（LTA）作为我们的毒素选择。我们的研究结果表明，LPS和LTA并不影响MSC的增殖，但延长LPS的挑战上调骨髓间充质干细胞的成骨分化，碱性磷酸酶活性和钙沉积评估。由于Toll样受体（TLR），特别是TLR4和TLR2，分别对细胞对LPS和LTA的反应是重要的，我们通过定量PCR连续评估了它们在从MSC到成骨细胞中的表达谱。我们发现在成骨分化过程中，MSC衍生的骨祖细胞在第12天逐渐表达TLR2和TLR4。但在长时间与LPS孵育下，MSC衍生的骨祖细胞的TLR2和TLR4基因表达降低。这种对LPS的特殊反应表明，当MSC连续暴露于细菌时，可能存在一种适应机制。总之，我们的研究结果支持使用人MSC作为生物移植物的潜力，即使在富含细菌毒素的环境下。
Human mesenchymal stromal cells (MSCs, also known as mesenchymal stem cells) are multipotent cells with potential therapeutic value. Owing to their osteogenic capability, MSCs may be clinically applied for facilitating osseointegration in dental implants or orthopedic repair of bony defect. However, whether wound infection or oral microflora may interfere with the growth and osteogenic differentiation of human MSCs remains unknown. This study investigated whether proliferation and osteogenic differentiation of MSCs would be affected by potent gram-positive and gram-negative derived bacterial toxins commonly found in human settings. We selected lipopolysaccharide (LPS) from Escherichia coli and lipoteichoic acid (LTA) from Streptococcus pyogenes as our toxins of choice. Our findings showed both LPS and LTA did not affect MSC proliferation, but prolonged LPS challenge upregulated the osteogenic differentiation of MSCs, as assessed by alkaline phosphatase activity and calcium deposition. Because toll-like receptors (TLRs), in particularly TLR4 and TLR2, are important for the cellular responsiveness to LPS and LTA respectively, we evaluated their expression profiles serially from MSCs to osteoblasts by quantitative PCR. We found that during osteogenic differentiation, MSC-derived osteoprogenitors gradually expressed TLR2 and TLR4 by Day 12. But under prolonged incubation with LPS, MSC-derived osteoprogenitors had reduced TLR2 and TLR4 gene expression. This peculiar response to LPS suggests a possible adaptive mechanism when MSCs are subjected to continuous exposure with bacteria. In conclusion, our findings support the potential of using human MSCs as a biological graft, even under a bacterial toxin-rich environment.
登录
查看更多内容
影响因子：
3.1
作者：
Gasper, NA;Petty, CC;Bost, KL
通讯作者：
Bost, KL
影响因子：
--
作者：
Asai, Y;Hirokawa, Y;Ogawa, T
通讯作者：
Ogawa, T
影响因子：
4.4
作者：
Itoh, K;Udagawa, N;Takahashi, N
通讯作者：
Takahashi, N
影响因子：
4.1
作者：
Bruder, SP;Horowitz, MC;Haynesworth, SE
通讯作者：
Haynesworth, SE
影响因子：
7.6
作者：
Chang, J;Zhang, C;Wang, CY
通讯作者：
Wang, CY