Effect of Heparan Sulfate on Vasculogenesis and Dentinogenesis of Dental Pulp Stem Cells

IF 3.5 2区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Journal of endodontics Pub Date : 2024-08-01 DOI:10.1016/j.joen.2024.04.015
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Abstract

Introduction

Heparan sulfate (HS) is a major component of dental pulp tissue. We previously reported that inhibiting HS biosynthesis impedes endothelial differentiation of dental pulp stem cells (DPSCs). However, the underlying mechanisms by which exogenous HS induces DPSC differentiation and pulp tissue regeneration remain unknown. This study explores the impact of exogenous HS on vasculogenesis and dentinogenesis of DPSCs both in vitro and in vivo.

Methods

Human-derived DPSCs were cultured in endothelial and odontogenic differentiation media and treated with HS. Endothelial differentiation of DPSCs was investigated by real-time polymerase chain reaction and capillary sprouting assay. Odontogenic differentiation was assessed through real-time polymerase chain reaction and detection of mineralized dentin-like deposition. Additionally, the influence of HS on pulp tissue was assessed with a direct pulp capping model, in which HS was delivered to exposed pulp tissue in rats. Gelatin sponges were loaded with either phosphate-buffered saline or 101–102 μg/mL HS and placed onto the pulp tissue. Following a 28-day period, tissues were investigated by histological analysis and micro–computed tomography imaging.

Results

HS treatment markedly increased expression levels of key endothelial and odontogenic genes, enhanced the formation of capillary-like structures, and promoted the deposition of mineralized matrices. Treatment of exposed pulp tissue with HS in the in vivo pulp capping study induced formation of capillaries and reparative dentin.

Conclusions

Exogenous HS effectively promoted vasculogenesis and dentinogenesis of DPSCs in vitro and induced reparative dentin formation in vivo, highlighting its therapeutic potential for pulp capping treatment.

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硫酸肝素对牙髓干细胞血管生成和牙本质生成的影响
简介硫酸肝素(HS)是牙髓组织的主要成分。我们以前曾报道过,抑制 HS 的生物合成会阻碍牙髓干细胞(DPSCs)的内皮分化。然而,外源性HS诱导DPSC分化和牙髓组织再生的潜在机制仍然未知。本研究探讨了外源性HS在体外和体内对DPSCs血管生成和牙本质生成的影响。通过实时 PCR 和毛细血管发芽试验研究 DPSCs 的内皮分化。通过实时 PCR 和矿化牙本质样沉积检测来评估牙本质分化。此外,还通过直接牙髓覆盖模型评估了 HS 对牙髓组织的影响。在明胶海绵中加入磷酸盐缓冲生理盐水或 101-102 μg/mL HS,并将其置于牙髓组织上。28 天后,通过组织学分析和显微 CT 成像对组织进行研究:结果:HS 处理显著提高了关键内皮和牙源性基因的表达水平,增强了毛细血管样结构的形成,并促进了矿化基质的沉积。在体内牙髓覆盖研究中,用 HS 处理暴露的牙髓组织可诱导毛细血管和修复性牙本质的形成:结论:外源性HS能有效促进体外DPSCs的血管生成和牙本质生成,并诱导体内修复性牙本质的形成,凸显了其在牙髓覆盖治疗中的治疗潜力。
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来源期刊
Journal of endodontics
Journal of endodontics 医学-牙科与口腔外科
CiteScore
8.80
自引率
9.50%
发文量
224
审稿时长
42 days
期刊介绍: The Journal of Endodontics, the official journal of the American Association of Endodontists, publishes scientific articles, case reports and comparison studies evaluating materials and methods of pulp conservation and endodontic treatment. Endodontists and general dentists can learn about new concepts in root canal treatment and the latest advances in techniques and instrumentation in the one journal that helps them keep pace with rapid changes in this field.
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