Oral supplementation with Lactiplantibacillus plantarum 6.2 in rats enhances bone and epithelial tissue repair by inhibiting NF-κB protein and promoting extracellular matrix synthesis via TGF-β

大鼠口服补充植物乳杆菌6.2可通过抑制NF-κB蛋白和促进TGF-β介导的细胞外基质合成,增强骨骼和上皮组织的修复。

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Abstract

BACKGROUND: This study aimed to investigate the healing and anti-inflammatory potential of the Lactiplantibacillus plantarum 6.2 (Lp62) strain, administered orally in a murine model of medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: Twenty male Wistar rats (N = 20) were randomly assigned to four groups (n = 5 per group): negative control (BASAL), healthy rats supplemented with Lp62 (LAC), experimental osteonecrosis (ONE), and osteonecrosis supplemented with Lp62 (ONE+LAC). Over an 8-week period, MRONJ was induced by intraperitoneal injections of zoledronic acid (250 μg/kg), except in the BASAL group, which received sterile 0.9% saline solution. This was followed by extraction of the left mandibular first molar. Lp62 supplementation (10⁹ CFU/mL) was administered daily by oral gavage during the 3rd and 7th weeks. At the end of the experimental period, animals were euthanized, and mandibles were examined macroscopically for exposed bone and epithelial closure. Histological evaluation included hematoxylin-eosin and Masson's trichrome staining, while immunohistochemical analysis was performed using anti-NF-κB and anti-TGF-β antibodies. Macroscopic and histomorphometric data were analyzed by one-way ANOVA followed by Tukey's or Dunnett's post hoc tests (p < 0.05). RESULTS: Epithelial closure and osteocyte preservation were evident in the BASAL, LAC, and ONE+LAC groups. In contrast, the ONE group exhibited no repair and showed higher NF-κB immunolabeling. Extracellular matrix (ECM) deposition was more pronounced in the Lp62-supplemented groups, which also demonstrated increased TGF-β immunolabeling. CONCLUSION: Oral supplementation with Lp62 promoted bone and epithelial regeneration, reduced NF-κB immunolabeling, and upregulated TGF-β in mandibular tissues, suggesting significant anti-inflammatory and reparative potential in experimental MRONJ lesions in rats.

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