Role of hyaluronan in regulating self-renewal and osteogenic differentiation of mesenchymal stromal cells and pre-osteoblasts.
Role of hyaluronan in regulating self-renewal and osteogenic differentiation of mesenchymal stromal cells and pre-osteoblasts.
复制标题
DOI：
10.1007/s00784-020-03259-8
复制
发表时间：
2020-11
影响因子：
3.4
通讯作者：
Sculean A
中科院分区：
文献类型：
--
作者：
Asparuhova MB;Chappuis V;Stähli A;Buser D;Sculean A
本研究的目的是研究两种透明质酸（HA）制剂对成骨细胞前体成骨潜能的影响。采用5-溴-20-脱氧尿苷（BrdU）法测定ha处理的间充质基质ST2和成骨前MC3T3-E1细胞的增殖率。通过定量逆转录聚合酶链反应（qRT-PCR）和免疫印迹技术分析ha处理细胞中编码成骨分化标志物、关键生长因子和干性因子的基因表达以及下游信号通路的激活。该研究强烈刺激了骨祖细胞的生长，增强了编码骨基质蛋白的基因的表达。然而，晚期成骨分化标志物的表达明显受到抑制，并伴有骨形态发生蛋白（BMP）信号传导降低。HA处理后，转化生长因子-β1 （TGF-β1）和成纤维细胞生长因子-1 （FGF-1）编码基因的表达以及下游信号分子Smad2和Erk1/2的磷酸化均增强。我们观察到，在ha处理的细胞中，转录因子Sox2及其直接转录靶点和关键干性基因Yap1和Bmi1显著上调。此外，典型Wnt信号通路的主要靶点表达降低，而该通路的抑制剂则显著上调。我们检测到ha处理的细胞中活性β-连环蛋白水平下降，这是由于β-连环蛋白被磷酸化，从而成为降解的目标。透明质酸强烈诱导骨祖细胞的生长并维持其干性，从而可能调节口腔重建手术后骨再生过程中自我更新和分化之间的平衡。在种植或牙周重建手术中，将透明质酸添加到缺损骨或骨缺损中可能是一种可行的方法，可以在不失去成体干细胞复制和分化能力的情况下扩增成体干细胞。本文的在线版本（10.1007/s00784-020-03259-8）包含补充资料，仅供授权用户使用。
The aim of the study was to investigate the impact of two hyaluronan (HA) formulations on the osteogenic potential of osteoblast precursors. Proliferation rates of HA-treated mesenchymal stromal ST2 and pre-osteoblastic MC3T3-E1 cells were determined by 5-bromo-20-deoxyuridine (BrdU) assay. Expression of genes encoding osteogenic differentiation markers, critical growth, and stemness factors as well as activation of downstream signaling pathways in the HA-treated cells were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunoblot techniques. The investigated HAs strongly stimulated the growth of the osteoprogenitor lines and enhanced the expression of genes encoding bone matrix proteins. However, expression of late osteogenic differentiation markers was significantly inhibited, accompanied by decreased bone morphogenetic protein (BMP) signaling. The expression of genes encoding transforming growth factor-β1 (TGF-β1) and fibroblast growth factor-1 (FGF-1) as well as the phosphorylation of the downstream signaling molecules Smad2 and Erk1/2 were enhanced upon HA treatment. We observed significant upregulation of the transcription factor Sox2 and its direct transcription targets and critical stemness genes, Yap1 and Bmi1, in HA-treated cells. Moreover, prominent targets of the canonical Wnt signaling pathway showed reduced expression, whereas inhibitors of the pathway were considerably upregulated. We detected decrease of active β-catenin levels in HA-treated cells due to β-catenin being phosphorylated and, thus, targeted for degradation. HA strongly induces the growth of osteoprogenitors and maintains their stemness, thus potentially regulating the balance between self-renewal and differentiation during bone regeneration following reconstructive oral surgeries. Addition of HA to deficient bone or bony defects during implant or reconstructive periodontal surgeries may be a viable approach for expanding adult stem cells without losing their replicative and differentiation capabilities. The online version of this article (10.1007/s00784-020-03259-8) contains supplementary material, which is available to authorized users.
登录
查看更多内容
DOI：
10.4103/1947-2714.112473
发表时间：
2013-05
期刊：
North American journal of medical sciences
影响因子：
--
作者：
Dahiya P;Kamal R
通讯作者：
Kamal R
DOI：
10.1038/bonekey.2013.171
发表时间：
2013-10-02
期刊：
BoneKEy reports
影响因子：
--
作者：
Guntur, Anyonya R;Rosen, Clifford J
通讯作者：
Rosen, Clifford J
影响因子：
7.3
作者：
Cowman MK;Lee HG;Schwertfeger KL;McCarthy JB;Turley EA
通讯作者：
Turley EA
影响因子：
5.3
作者：
Ambrosetti, Davide;Holmes, Greg;Basilico, Claudio
通讯作者：
Basilico, Claudio
影响因子：
4.1
作者：
Holmes, Greg;Bromage, Timothy G.;Basilico, Claudio
通讯作者：
Basilico, Claudio