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Dual Roles of Melatonin in Rescuing Inflammation-caused Cell Mitochondrial Dysfunction and Cementoblastic Differentiation

ABSTRACT: Inflammation-induced mitochondrial dysfunction functionally impairs periodontal ligament stem cells (PDLSCs) and hinders their therapeutic efficacy for periodontal regeneration. Melatonin, a mitochondrion-targeted molecule, is considered a promising anti-inflammatory agent in therapeutics, but whether melatonin protects PDLSC cementoblastic differentiation against inflammation-induced damage and the underlying molecular mechanisms remain unclear. In this study, we confirmed that melatonin rescued PDLSC cementoblastic dysfunction across an inflammatory environment, and the melatonin-induced recovery was linked to the ameliorated mitochondrial function of the treated PDLSCs. Next, an interaction between LINC01444 and HSPD1 was identified as a mechanism mediating such melatonin-caused mitochondrial changes in terms of lncRNA microarray analysis, mass spectrometry and functional studies. In this context, suppressing LINC01444 was found to increase the total and cytoplasmic expression of HSPD1 protein, and in turn, the cell mitochondria function was ameliorated. We further revealed another route where melatonin was able to inhibit m6A modification of LINC01444 (mediated by METTL3 and IGF2BP2), thereby the stability and expression of LINC01444 were largely decreased. Our data indicate that LINC01444 is a key target involved in melatonin-rescued cell mitochondrial function and cementoblastic differentiation, wherein melatonin not only prevents LINC01444 from interacting with HSPD1 to exert its damage to PDLSCs, but also inhibits LINC01444 from modifying by m6A to maintain its stability and expression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE245656 | GEO | 2026/06/18

REPOSITORIES: GEO

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