mmu_circ_0000217通过miR-3064-3p/DKK1轴促进牙骨质细胞成骨分化机制

Abstract

Periodontitis leads to irreversible periodontal tissue damage, and current treatments lack sufficient regenerative capacity. This study investigated the role of mmu_circ_0000217 in osteogenic differentiation of OCCM-30 cementoblastic cells and its underlying mechanism, aiming to provide a theoretical basis for periodontal tissue regeneration. This study first identified the upregulated expression of mmu_circ_0000217 during osteogenic differentiation of OCCM-30 cells using high-throughput sequencing. The impact of mmu_circ_0000217 on cell proliferation and apoptosis was evaluated in OCCM-30 cells by modulating its expression and using CCK-8 assays and TUNEL staining. Morphological changes related to mineralization and differentiation were examined using Alkaline Phosphatase (ALP) and Alizarin Red S staining (ARS). Osteogenic gene and protein expressions were analyzed with QPCR and Western blotting, which also detected JAK-STAT3 signaling pathway activation. High-throughput sequencing identified mmu_circ_0000217 as the most significantly upregulated circRNA during osteogenic induction. Functional experiments demonstrated that mmu_circ_0000217 overexpression significantly enhanced cell proliferation, inhibited apoptosis, and potentiated mineralization, as evidenced by increased ALP activity and Alizarin Red S staining. Conversely, its knockdown produced the opposite effects. Mechanistically, mmu_circ_0000217 functioned as a molecular sponge for miR-3064-3p, which led to the derepression of its target, DKK1, and consequent activation of the JAK-STAT3 signaling pathway. Mmu_circ_0000217 activated the JAK-STAT3 signaling pathway by adsorbing miR-3064-3p, promoted cell proliferation, inhibited apoptosis, and enhanced osteoblast differentiation. These findings enhance our understanding of the molecular mechanisms behind periodontal tissue regeneration.