Differential molecular profiles and associated functionalities characterize connective tissue grafts obtained at different locations and depths in the human palate

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
Maria B. Asparuhova, Xiaoqing Song, Dominic Riedwyl, Geert van Geest, Dieter D. Bosshardt, Anton Sculean
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Abstract

The present study aimed to assess the molecular profiles of subepithelial connective tissue grafts (CTGs) obtained at different locations and depths in the human palate. Sixty-four CTGs belonging to anterior deep (AD), anterior superficial (AS), posterior deep (PD), and posterior superficial (PS) groups were subjected to RNA-Sequencing and their transcriptomes were analyzed computationally. Functional correlations characterizing the CTG groups were validated by cell biological experiments using primary human palatal fibroblasts (HPFs) extracted from the CTGs. A clearly more pronounced location-dependent than depth-dependent difference between the grafts, with a minimal number of genes (4) showing no dependence on the location, was revealed. Epithelial, endothelial, and monocytic cell migration was strongly (P < 0.001) potentiated by AD- and PS-HPFs. Moreover, significantly increased expression of genes encoding C-C and C-X-C motif chemokine ligands as well as significantly (P < 0.01) activated p38 signaling suggested immunomodulatory phenotype for AD- and PS-HPFs. Increased growth factor gene expression and significantly activated (P < 0.001) Erk and Akt signaling in HPFs originating from A-CTGs implied their involvement in cell survival, proliferation, and motility. Prominent collagen-rich expression profile contributing to high mechanical stability, increased osteogenesis-related gene expression, and strongly activated (P < 0.001) Smad1/5/8 signaling characterized HPFs originating from P-CTGs. The present data indicate that in humans, differences between palatal CTGs harvested from different locations and depths appear to be location- rather than depth-dependent. Our findings provide the basis for future personalization of the therapeutic strategy by selecting an optimal graft type depending on the clinical indications.

Abstract Image

人腭不同位置和深度的结缔组织移植物具有不同的分子特征和相关功能特性
本研究旨在评估人腭不同位置和深度的上皮下结缔组织移植物(CTG)的分子特征。研究人员对属于前深(AD)、前浅(AS)、后深(PD)和后浅(PS)组的64个CTG进行了RNA测序,并对其转录组进行了计算分析。使用从 CTGs 提取的原代人腭成纤维细胞(HPFs)进行细胞生物学实验,验证了 CTG 组的功能相关性特征。结果显示,移植物之间的差异明显取决于位置而非深度,只有极少数基因(4 个)与位置无关。上皮细胞、内皮细胞和单核细胞的迁移受到 AD-HPFs 和 PS-HPFs 的强烈促进(P < 0.001)。此外,编码 C-C 和 C-X-C motif 趋化因子配体的基因表达明显增加,p38 信号的激活也明显增加(P < 0.01),这表明 AD-HPFs 具有免疫调节表型。在源自 A-CTG 的 HPFs 中,生长因子基因表达增加,Erk 和 Akt 信号明显激活(P < 0.001),这意味着它们参与了细胞的存活、增殖和运动。源自 P-CTG 的 HPF 具有显著的富含胶原蛋白的表达谱,这有助于提高机械稳定性、增加成骨相关基因的表达以及强烈激活(P < 0.001)Smad1/5/8 信号传导。本研究数据表明,在人类中,从不同位置和深度采集的腭CTG之间的差异似乎与位置而非深度有关。我们的研究结果为今后根据临床适应症选择最佳移植类型的个性化治疗策略奠定了基础。
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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
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