Bone morphogenetic protein-4 induced matrix turnover and osteogenic differentiation-related molecules of stem cells from apical papilla and its associated ALK/Smad signaling

IF 3.4 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Dental Sciences Pub Date : 2025-01-01 DOI:10.1016/j.jds.2024.11.002

Mei-Chi Chang , Yi-Chi Chao , Yi-Chieh Chen , Hsueh-Wei Chang , Bor-Hao Zhong , Yu-Hwa Pan , Jiiang-Huei Jeng , Hsiao-Hua Chang

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引用次数: 0

Abstract

Background/purpose

Revascularization procedures are used over apexification to treat teeth with necrotic pulp tissues and incomplete root formation. Clinically, inducing proliferation, migration, matrix deposition, and differentiation of stem cells from apical papilla (SCAPs) are critical for pulp regeneration. The study aimed to elucidate the impact of bone morphogenetic protein-4 (BMP-4) on plasminogen activation molecules and the osteogenic/odontogenic differentiation of SCAPs, as well as understand the related signaling mechanisms.

Materials and methods

SCAPs were exposed to BMP-4 with or without signal transduction inhibitors. Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. mRNA levels were quantified using real-time PCR. Protein expression in SCAPs was analyzed through immunofluorescent staining or western blotting. Cellular protein production was measured with enzyme-linked immunosorbent assay.

Results

BMP-4 induced suppressor of mother against decapentaplegic (Smad)1/5/8 and Smad2/3 phosphorylation and activation. It also promoted higher expression of osteogenic and odontogenic markers, including Osterix, N-cadherin, and secreted protein acidic and rich in cysteine (SPARC), in SCAPs. Additionally, BMP-4 stimulated connective tissue growth factor (CTGF), plasminogen activator inhibitor-1 (PAI-1), and urokinase plasminogen activator receptor (uPAR) expression, but inhibited uPA expression and production in SCAPs, indicating its role in matrix remodeling and cell migration. Inhibition of Smad2/3 with SB431542 and Smad1/5/8 with LDN193189 attenuated the BMP-4-induced expression Osx, N-cadherin, CTGF, SPARC, uPAR and PAI-1.

Conclusion

These results indicate that BMP-4 stimulates the osteogenic and odontogenic differentiation of SCAPs by regulating matrix turnover and mineralization-related proteins. Furthermore, these processes are associated with the induction of Smad2/3 and Smad1/5/8 of SCAPs by BMP-4.

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背景/目的：血管再造手术用于治疗牙髓组织坏死和牙根未完全形成的牙齿。在临床上，诱导牙根尖乳头干细胞（SCAPs）的增殖、迁移、基质沉积和分化对牙髓再生至关重要。该研究旨在阐明骨形态发生蛋白-4（BMP-4）对纤溶酶原激活分子和SCAPs成骨/成牙根分化的影响，并了解相关的信号机制：在使用或不使用信号转导抑制剂的情况下，将 SCAPs 暴露于 BMP-4。使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑测定法评估细胞活力。通过免疫荧光染色或 Western 印迹分析 SCAPs 中的蛋白质表达。用酶联免疫吸附法测定细胞蛋白质的生成：结果：BMP-4 能诱导癸型截瘫母细胞抑制因子（Smad）1/5/8 和 Smad2/3 的磷酸化和活化。它还能促进成骨和牙源性标志物在 SCAPs 中的高表达，包括 Osterix、N-cadherin 和富含半胱氨酸的酸性分泌蛋白（SPARC）。此外，BMP-4 还能刺激结缔组织生长因子（CTGF）、纤溶酶原激活剂抑制剂-1（PAI-1）和尿激酶纤溶酶原激活剂受体（uPAR）的表达，但却能抑制 SCAPs 中 uPA 的表达和产生，这表明它在基质重塑和细胞迁移中发挥作用。用 SB431542 抑制 Smad2/3，用 LDN193189 抑制 Smad1/5/8，可减轻 BMP-4 诱导的 Osx、N-钙粘蛋白、CTGF、SPARC、uPAR 和 PAI-1 的表达：这些结果表明，BMP-4 可通过调节基质周转和矿化相关蛋白来刺激 SCAPs 的成骨和牙源性分化。此外，这些过程与 BMP-4 诱导 SCAPs 的 Smad2/3 和 Smad1/5/8 有关。

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来源期刊

Journal of Dental Sciences 医学-牙科与口腔外科

CiteScore

5.10

自引率

14.30%

发文量

348

审稿时长

6 days

期刊介绍： he Journal of Dental Sciences (JDS), published quarterly, is the official and open access publication of the Association for Dental Sciences of the Republic of China (ADS-ROC). The precedent journal of the JDS is the Chinese Dental Journal (CDJ) which had already been covered by MEDLINE in 1988. As the CDJ continued to prove its importance in the region, the ADS-ROC decided to move to the international community by publishing an English journal. Hence, the birth of the JDS in 2006. The JDS is indexed in the SCI Expanded since 2008. It is also indexed in Scopus, and EMCare, ScienceDirect, SIIC Data Bases. The topics covered by the JDS include all fields of basic and clinical dentistry. Some manuscripts focusing on the study of certain endemic diseases such as dental caries and periodontal diseases in particular regions of any country as well as oral pre-cancers, oral cancers, and oral submucous fibrosis related to betel nut chewing habit are also considered for publication. Besides, the JDS also publishes articles about the efficacy of a new treatment modality on oral verrucous hyperplasia or early oral squamous cell carcinoma.