Stage-Dependent Regulation of Dental Pulp Stem Cell Odontogenic Differentiation by Transforming Growth Factor-β1.
Stage-Dependent Regulation of Dental Pulp Stem Cell Odontogenic Differentiation by Transforming Growth Factor-β1.
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DOI：
10.1155/2022/2361376
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发表时间：
2022
影响因子：
4.3
通讯作者：
He, Wenxi
中科院分区：
文献类型：
--
作者：
Bai, Yu;Liu, Xin;Li, Junqing;Wang, Zhihua;Guo, Qian;Xiao, Min;Cooper, Paul R.;Yu, Qing;He, Wenxi
转化生长因子-β1（transforminggrowthfactor-β 1，TGF-β1）是一种重要的多功能细胞因子，对干细胞分化具有双重作用。然而，TGF-β1在牙髓干细胞向牙源性分化中的作用尚不完全清楚。在本研究中，我们初步研究了一系列浓度（0.1-5 ng/mL）的TGF-β1对DPSC增殖、细胞周期和凋亡的影响。随后，通过碱性磷酸酶（ALP）活性测定和茜素红S（ARS）染色检测不同浓度和时间点的TGF-β1对牙向分化的影响。采用实时定量聚合酶链反应（qRT-PCR）和蛋白质印迹分析分别测定牙/骨分化相关基因和蛋白的表达水平。对于体内研究，通过Masson三色和von Kossa染色评估新形成的组织。TGF-β1呈浓度和时间依赖性抑制DPSCs增殖（p < 0.05），诱导细胞周期阻滞，但不影响细胞凋亡。随着TGF-β1浓度的增加，ALP活性增强，ARS活性逐渐降低，同时伴有牙/骨分化早期标志基因表达增强，晚期矿化标志基因表达降低（p < 0.05）。TGF-β1处理组ALP表达升高，直到14天，ARS染色强度在14和21天减弱（p < 0.05）。与对照组相比，TGF-β1处理组的胶原含量丰富，但无矿化组织。这些结果表明，TGF-β1促进DPSCs早期牙向分化，同时抑制后期矿化过程。
Transforming growth factor-β1 (TGF-β1) is an important multifunctional cytokine with dual effects on stem cell differentiation. However, the role of TGF-β1 on odontogenic differentiation of dental pulp stem cells (DPSCs) remains to be entirely elucidated. In the present study, we initially investigated the effect of TGF-β1 at a range of concentrations (0.1-5 ng/mL) on the proliferation, cell cycle, and apoptosis of DPSCs. Subsequently, to determine the effect of TGF-β1 on odontogenic differentiation, alkaline phosphatase (ALP) activity and Alizarin Red S (ARS) staining assays at different concentrations and time points were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were used to determine the levels of odonto-/osteo-genic differentiation-related gene and protein expression, respectively. For in vivo studies, newly formed tissue was assessed by Masson's trichrome and von Kossa staining. Data indicated that TGF-β1 inhibited DPSCs proliferation in a concentration-and time-dependent manner (p < 0.05) and induced cell cycle arrest but did not affect apoptosis. ALP activity was enhanced, while ARS reduced gradually with increasing TGF-β1 concentrations, accompanied by increased expression of early marker genes of odonto-/osteo-genic differentiation and decreased expression of late-stage mineralization marker genes (p < 0.05). ALP expression was elevated in the TGF-β1-treatment group until 14 days, and the intensity of ARS staining was attenuated at days 14 and 21 (p < 0.05). Compared with the control group, abundant collagen but no mineralized tissues were observed in the TGF-β1-treatment group in vivo. Overall, these findings indicate that TGF-β1 promotes odontogenic differentiation of DPSCs at early-stage while inhibiting later-stage mineralization processes.
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影响因子：
5.1
作者：
Almushayt, A;Narayanan, K;George, A
通讯作者：
George, A
影响因子：
5.6
作者：
Amarasekara DS;Kim S;Rho J
通讯作者：
Rho J
影响因子：
4.2
作者：
Ivica, Anja;Deari, Shengjile;Zehnder, Matthias
通讯作者：
Zehnder, Matthias
影响因子：
3
作者：
Li, Yucheng;Lu, Xin;Shi, Junnan
通讯作者：
Shi, Junnan
DOI：
10.1089/ten.tec.2017.0400
发表时间：
2018-03
期刊：
Tissue engineering. Part C, Methods
影响因子：
--
作者：
Macri-Pellizzeri L;De Melo N;Ahmed I;Grant D;Scammell B;Sottile V
通讯作者：
Sottile V