Pre-operative clinical signs and symptoms.

BackgroundNumerous studies reported that the healing after surgical endodontic retreatment is influenced by multiple factors which include the genetic profile of the patient, epigenetics, and immune responses. The genes which are primarily responsible for the healing potential in different individuals are those which are involved in the regulation of the cytoskeleton and cellular adhesion which subsequently affects bone deposition and healing. Integrins are cell-surface molecules, possess a key role in the cytoskeleton and cellular adhesion. Integrin Subunit Alpha 1 (ITGA1) is one among the integrin family and helps in regulating the Epidermal Growth Factor receptor (EGFR) pathway, consequently affects proliferation and healing. The objectives of the study were to identify mutations in the cytoplasmic domain of Integrin Subunit Alpha 1 (ITGA1), to assess the expression of activated EGFR, EGFRPhospho and TC-PTP in the periapical wound and to correlate these mutations and expression patterns with periapical wound healing.Methods and findingsThirty-seven patients between ages 18–60 years reported chronic apical periodontitis of single-rooted anterior teeth with periapical radiolucency, equal or greater than 4 mm or periapical lesion in an open apex of single-rooted teeth due to trauma were included in the study from 01st June 2018 till 31st October 2019. Patients with persistent radiolucency after primary root canal treatment and endodontic retreatment were kept on follow-up for 3–4 months surgical endodontic treatment was performed in cases with persistent periapical lesions of 4mm or more in diameter. Periapical lesion sample was collected and used for (1) histo-pathological analysis after Hematoxylin & Eosin staining, (2) total DNA extraction for ITGA1 cytoplasmic domain mutational analysis and immunohistochemistry for EGFR and TCPTP. A positive correlation was observed between the expression levels of EGFRPhospho and the healing of periapical lesions. Moreover, a negative weak correlation was observed between the expression levels of EGFR and TCPTP and the healing of periapical lesions. Out of nine sequences of cytoplasmic domain of ITGA1 which were analyzed, none of them was detected with SNP.ConclusionHigher expression levels of EGFRPhospho and lower expression levels of EGFR and TCPTP were associated with patients with good healing potential in periapical area. However, immunohistochemistry scores were statistically insignificant to draw any conclusion.

背景 已有多项研究表明，外科牙髓再治疗后的愈合效果受多种因素影响，包括患者的遗传特征、表观遗传学及免疫应答。调控不同个体愈合潜能的核心基因，多参与细胞骨架调控与细胞黏附过程，此类基因可进一步影响骨沉积与组织愈合。整合素是一类细胞表面分子，在细胞骨架调控及细胞黏附过程中发挥关键作用。整合素亚基α1（Integrin Subunit Alpha 1, ITGA1）隶属于整合素家族，可调控表皮生长因子受体（Epidermal Growth Factor receptor, EGFR）通路，进而影响细胞增殖与组织愈合。本研究的目的为：检测整合素亚基α1（ITGA1）胞质结构域的突变情况，评估根尖周创面中活化型EGFR、磷酸化EGFR（EGFRPhospho）及T细胞蛋白酪氨酸磷酸酶（TC-PTP）的表达水平，并将上述突变与表达模式与根尖周创面愈合情况进行关联分析。方法与结果 本研究于2018年6月1日至2019年10月31日期间纳入37名年龄18~60岁的患者，纳入标准为：单根前牙慢性根尖周炎伴根尖周透射影，且透射影范围≥4mm；或因外伤导致单根牙开放根尖出现根尖周病变。对于初次根管治疗及牙髓再治疗后仍存在持续性透射影的患者，先予以3~4个月随访，针对直径≥4mm的持续性根尖周病变患者实施外科牙髓治疗。收集根尖周病变样本，用于以下检测：（1）经苏木精-伊红（Hematoxylin & Eosin, HE）染色后的组织病理学分析；（2）提取总DNA以开展ITGA1胞质结构域突变检测，同时采用免疫组化法检测EGFR与TC-PTP的表达。研究结果显示：磷酸化EGFR的表达水平与根尖周病变的愈合程度呈正相关；此外，EGFR与TC-PTP的表达水平与根尖周病变的愈合程度呈弱负相关。对9份ITGA1胞质结构域序列进行分析后，未检测到单核苷酸多态性（Single Nucleotide Polymorphism, SNP）。结论 磷酸化EGFR高表达、EGFR与TC-PTP低表达的患者，其根尖周区域的愈合潜能更佳。但本次研究的免疫组化评分无统计学显著性，尚不足以得出确定性结论。