Matrix metalloproteinases system profile analysis and their endogenous inhibitors in children with periodontal diseases and various dysplasia phenotypes

B. N. Davydov, D. Domenyuk, T. Kochkonyan
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Abstract

Relevance. The search and development of modern non-invasive methods for early periodontal disease detection are of scientific and practical value for a personalized approach to disease course prognosis and explaining the choice of treatment tactics. Morphological immaturity, high intensity of anabolic processes, functional failure of neurohumoral, endocrine and immunological defence systems combined with an imbalance between the synthesis and degradation of extracellular matrix components in children with undifferentiated connective tissue disease (UCTD) significantly in-creases the risk of developing periodontal diseases. The available data on the activity of salivary matrix metalloproteinases (MMPs), which play a leading role in regulating connective tissue protein metabolism and bone remodelling mechanisms in children with UCTD of various degrees, are scarce and require further study.Purpose. The study aimed to explain the clinical, diagnostic and prognostic value of MMPs as markers of inflammatory periodontal diseases in children with UCTD and dysplastic disorders of various severity.Material and methods. The study included 67 children with UCTD (main group) and 34 children of health groups I and II (comparison group) aged 12-17. The UCTD severity was established according to the diagnostic criteria by L. N. Abbakumova (2006) and a scale for assessing the significance of phenotypic and visceral signs. The main group was divided into two subgroups: Subgroup 1 (n = 38) – children with mild and moderate UCTD; Subgroup 2 (n=29) – children with severe UCTD. The studied groups had their periodontal status assessed, as well as the concentration of MMP-1, MMP-2, MMP-8, MMP-9 and their tissue inhibitors (TIMP-1, TIMP-2) in the oral fluid identified using the enzyme immunoassay, along with calculation done for the MMP ⁄ TIMP coefficients that set a balance between the degradation and synthesis of collagen.Results. The children with phenotypic signs of UCTD in the oral fluid appeared to show a statistically significant increase in the MMP-1, MMP-2, MMP-8, and MMP-9 levels and an imbalanced ratio in MMP-1⁄TIMP-1, MMP-2⁄TIMP-2, MMP-8⁄TIMP-1, MMP-9⁄TIMP-1, compared with health groups I, II. An increase in the MMP-1, MMP-2, and MMP-8 concentrations, along with dominating expression of MMP-9 over TIMP-1 in the oral fluid of children of Subgroup 2, causes an increase in intensity and prevalence of periodontal diseases compared to the patients in Sub-group 1 and comparison group.Conclusion. Thus, when children with UCTD don’t demonstrate an increase in specific tissue inhibitors TIMP-1 and TIMP-2 in their oral fluid, along with an increase in the levels of the respective matrixins is the key pathogenetic factor in the degradation of extracellular matrix proteins, which causes a depressing impact on the proliferative activity in the periodontal set of tissues.
牙周病和各种发育不良表型儿童的基质金属蛋白酶系统概况分析及其内源性抑制剂
相关性。寻找和开发早期牙周病检测的现代非侵入性方法,对于个性化病程预后和治疗策略的选择具有科学和实用价值。未分化结缔组织病(UCTD)患儿的形态不成熟、高强度的合成代谢过程、神经体液、内分泌和免疫防御系统的功能衰竭,再加上细胞外基质成分合成和降解之间的不平衡,大大增加了患牙周病的风险。唾液基质金属蛋白酶(MMPs)在调节不同程度的未分化结缔组织病患儿的结缔组织蛋白代谢和骨重塑机制中发挥着主导作用,但有关唾液基质金属蛋白酶(MMPs)活性的现有数据却很少,需要进一步研究。该研究旨在解释 MMPs 作为不同严重程度的 UCTD 和发育不良儿童炎症性牙周疾病标志物的临床、诊断和预后价值。研究对象包括 67 名 UCTD 患儿(主要组)和 34 名健康组 I 和 II 患儿(对比组),年龄在 12-17 岁之间。UCTD 的严重程度是根据 L. N. Abbakumova(2006 年)的诊断标准以及表型和内脏体征重要性评估表确定的。主组被分为两个亚组:亚组 1(n=38)--轻度和中度牙周病患儿;亚组 2(n=29)--重度牙周病患儿。研究小组对牙周状况进行了评估,并使用酶免疫测定法确定了口腔液中 MMP-1、MMP-2、MMP-8、MMP-9 及其组织抑制剂(TIMP-1、TIMP-2)的浓度,同时计算了 MMP ⁄ TIMP 系数,该系数设定了胶原蛋白降解与合成之间的平衡。与健康组 I 和 II 相比,口腔液中有 UCTD 表型迹象的儿童的 MMP-1、MMP-2、MMP-8 和 MMP-9 水平出现了统计学意义上的显著增加,MMP-1⁄TIMP-1、MMP-2⁄TIMP-2、MMP-8⁄TIMP-1、MMP-9⁄TIMP-1 的比例失调。与亚组 1 和对比组相比,亚组 2 儿童口腔液中 MMP-1、MMP-2 和 MMP-8 的浓度增加,MMP-9 的表达超过了 TIMP-1,导致牙周疾病的强度和患病率增加。因此,当 UCTD 儿童口腔液中的特异性组织抑制剂 TIMP-1 和 TIMP-2 没有增加时,相应基质蛋白水平的增加是细胞外基质蛋白降解的关键致病因素,会对牙周组织的增殖活动产生抑制作用。
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