BACH1 regulates the proliferation and odontoblastic differentiation of human dental pulp stem cells.
BACH1 regulates the proliferation and odontoblastic differentiation of human dental pulp stem cells.
复制标题
BACH1调节人牙髓干细胞的增殖和成牙本质细胞分化
DOI：
10.1186/s12903-022-02588-2
复制
发表时间：
2022-11-24
期刊：
影响因子：
2.9
通讯作者：
Peng, B.
中科院分区：
文献类型：
--
作者：
Liu, C.;Yu, J.;Liu, B.;Liu, M.;Song, G.;Zhu, L.;Peng, B.
关键词：
维持生物和生理活性以及牙本质的形成是人类牙髓一生的主要任务之一。人牙髓干细胞（human dental pulp stem cells，hDPSCs）向成牙本质细胞分化具有牙髓再生和牙本质复合体重建的能力。对hDPSCs分化和增殖调控机制的研究有助于探索其潜在的临床应用价值。BTB和CNC同源物1（BACH 1）是参与多种细胞功能调节的转录阻遏物。本研究旨在探讨BACH 1对人牙髓干细胞体外增殖及向成牙本质细胞分化的影响。从提取的人前磨牙或第三磨牙获得hDPSC和牙髓组织。免疫组化法检测BACH 1的分布。采用qRT-PCR和Western blot检测BACH 1 mRNA和蛋白表达。BACH 1的表达通过稳定的慢病毒介导的转染来调节。采用细胞计数试剂盒-8法、5-乙炔基-2 '-脱氧尿苷法和流式细胞术检测细胞增殖和细胞周期。通过矿化标志物表达、碱性磷酸酶（ALP）活性和茜素红S染色评价成牙本质细胞分化能力。BACH 1在成牙本质细胞层的表达强于细胞丰富区。在成牙本质细胞分化过程中，BACH 1的总蛋白和核蛋白水平先下调后上调。BACH 1基因敲除可显著抑制细胞增殖，阻滞细胞周期，上调血红素加氧酶-1（HO-1）表达，降低ALP活性，减少钙沉积，下调矿化标志物的表达。HO-1抑制剂锡原卟啉IX的治疗未能挽救受损的牙本质/成骨分化能力。BACH 1过表达增加细胞增殖、ALP活性和矿化标记物的表达。我们的研究结果表明，BACH 1是一个重要的调节增殖和成牙本质细胞分化的hDPSCs在体外。操纵BACH 1表达可能提供促进hDPSC再生能力的机会。在线版本包含补充材料，可通过10.1186/s12903-022-02588-2获得。
The preservation of biological and physiological vitality as well as the formation of dentin are among the main tasks of human dental pulp for a life time. Odontoblastic differentiation of human dental pulp stem cells (hDPSCs) exhibits the capacity of dental pulp regeneration and dentin complex rebuilding. Exploration of the mechanisms regulating differentiation and proliferation of hDPSCs may help to investigate potential clinical applications. BTB and CNC homology 1 (BACH1) is a transcription repressor engaged in the regulation of multiple cellular functions. This study aimed to investigate the effects of BACH1 on the proliferation and odontoblastic differentiation of hDPSCs in vitro. hDPSCs and pulpal tissues were obtained from extracted human premolars or third molars. The distribution of BACH1 was detected by immunohistochemistry. The mRNA and protein expression of BACH1 were examined by qRT-PCR and Western blot analysis. BACH1 expression was regulated by stable lentivirus-mediated transfection. Cell proliferation and cell cycle were assessed by cell counting kit-8 assay, 5-Ethynyl-2'-deoxyuridine assay and flow cytometry. The expression of mineralization markers, alkaline phosphatase (ALP) activity and alizarin red S staining were conducted to assess the odontoblastic differentiation ability. BACH1 expression was stronger in the odontoblast layer than in the cell rich zone. The total and nuclear protein level of BACH1 during odontoblastic differentiation was downregulated initially and then upregulated gradually. Knockdown of BACH1 greatly inhibited cell proliferation, arrested cell cycle, upregulated the heme oxygenase-1 (HO-1) expression and attenuated ALP activity, decreased calcium deposits and downregulated the expression of mineralization markers. Treatment of Tin-protoporphyrin IX, an HO-1 inhibitor, failed to rescue the impaired odonto/osteogenic differentiation capacity. Overexpression of BACH1 increased cell proliferation, ALP activity and the expression of mineralization markers. Our findings suggest that BACH1 is an important regulator of the proliferation and odontoblastic differentiation of hDPSCs in vitro. Manipulation of BACH1 expression may provide an opportunity to promote the regenerative capacity of hDPSCs. The online version contains supplementary material available at 10.1186/s12903-022-02588-2.
登录
查看更多内容
影响因子：
2.1
作者：
Omura, S;Suzuki, H;Igarashi, K
通讯作者：
Igarashi, K
影响因子：
64.5
作者：
Lignitto, Luca;LeBoeuf, Sarah E.;Pagano, Michele
通讯作者：
Pagano, Michele
影响因子：
5.6
作者：
Lin, Tzu-Hung;Tang, Chih-Hsin;Yang, Rong-Sen
通讯作者：
Yang, Rong-Sen
影响因子：
5
作者：
Kulan, P.;Karabiyik, O.;Kargul, B.
通讯作者：
Kargul, B.
影响因子：
14.9
作者：
Jeon SM;Lim JS;Park SH;Kim HJ;Kim HR;Lee JH
通讯作者：
Lee JH