Role of miRNA-155 in the regulation of osteoclast differentiation mediated by MITF in stage III/IV periodontitis: a case-control study

J Genet Eng Biotechnol. 2022 Dec 2;20(1):161. doi: 10.1186/s43141-022-00441-1.

Abstract

Background: Monocyte-macrophage lineage cells are committed towards osteoclast differentiation in vitro by the downregulation of microphthalmia-induced transcription factor (MITF) by miRNA-155. Therefore, we aimed to evaluate miRNA-155 expression and explore the regulation of MITF by miRNA-155 during osteoclastogenesis in periodontitis.

Materials and methods: Ninety-eight subjects were recruited and categorized into the following: group I (cases)-systemically healthy with localized stage III/IV periodontitis (N = 49) and group II (controls)-systemically and periodontally healthy (N = 49). Gingival tissue samples were procured and qRT-PCR analysis was carried out for relative gene expression.

Results: The mean ΔCT of miRNA-155 expression was -1.04 ± 2.26 and -0.01 ± 1.4 respectively for groups I and II. There was a statistically significant difference in the miRNA-155 expression (P ≤ 0.01) between the groups. The mean ΔCT of MITF expression for groups I and II was 4.15± 2.16 and 3.51± 1.57 respectively with no significant difference (P > 0.01) between the groups. In the periodontitis group, miRNA-155 expression increased by fivefolds (P ≤ 0.01) whereas MITF expression showed no significant difference in the fold change between the groups (P > 0.01). The site-specific clinical parameters showed a statistically significant strong negative and positive correlation with the ΔCT and fold change values of miRNA-155 respectively in the total 98 samples (P < 0.01). miRNA-155 was able to discriminate between periodontal health and disease with a diagnostic accuracy of 96.9% (95%CI: 91.38-98.95) and the AUC was 0.98 (95%CI: 0.97-1.0, SE = 0.008, P < 0.001) in ROC analysis with a sensitivity of 93.8% (95%CI: 83.48-97.9) and specificity of 100% (95%CI: 92.73-100).

Conclusions: miRNA-155 was dysregulated and upregulated by fivefolds in periodontal disease. It can be used as a potential biomarker to discriminate between periodontal health and disease. No difference in the MITF gene expression was demonstrated between periodontal health and disease. The result suggested that miRNA-155 does not affect the expression of MITF gene in the process of osteoclastogenesis in localized stage III/IV periodontitis within this study design and limitations.

Keywords: MITF; Osteoclastogenesis; Periodontitis; miRNA-155; microRNA; qRT-PCR.