Journal of oral biosciences · 2026
Metformin suppresses periapical bone resorption in a mouse model of apical periodontitis in vivo and inhibits RANKL-induced osteoclastogenesis in vitro.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Alghamdi Faisal, Ren Chunmei, Tazawa Kento, Liu Shuaichen, Zhou Chuyi, Takahashi Junnosuke, Ishidori Masaharu, Ohshima Risa, Kawashima Nobuyuki, Okiji Takashi, Yahata Yoshio
Аннотация
OBJECTIVES: Metformin (MET), a widely used antidiabetic drug, has recently gained attention for its anti-bone-resorptive properties. This study evaluated these effects in apical periodontitis (AP) and explored its underlying molecular mechanisms particularly its role in osteoclastogenesis.
METHODS: AP was induced in the mandibular first molars of nine 6-week-old male C57BL/6 JJcl mice by pulp exposure for 21 days. MET (50 mg/kg/day) was administered intraperitoneally beginning 1 d before the procedure. Periapical bone resorption was evaluated using micro-computed tomography and tartrate-resistant acid phosphatase (TRAP) staining. In vitro, RAW264.7 murine macrophages were stimulated into osteoclasts using receptor activator of nuclear factor κB ligand (RANKL; 100 ng/mL) for 7 days, whereas the suppressive effect of MET (0.5 mM) on osteoclastogenesis was evaluated using TRAP staining. The mRNA expression of osteoclastogenesis-related genes was measured by real-time quantitative polymerase chain reaction. The effects of MET on extracellular signal-regulated kinase (ERK) and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) signaling were determined using western blotting and luciferase assays, respectively.
RESULTS: MET significantly reduced the lesion size and number of TRAP-positive osteoclasts in vivo at day 21. In vitro, MET significantly inhibited RANKL-induced osteoclastogenesis and decreased the number of TRAP-positive osteoclasts (≥3 nuclei). MET significantly suppressed the RANKL-induced mRNA expression of the osteoclastogenesis-related genes osteoclast-associated receptor, acid phosphatase 5, tartrate resistant, and osteoclast stimulatory transmembrane protein. Moreover, it reduced RANKL-induced p-ERK and NFATc1 signaling.
CONCLUSIONS: MET suppresses bone resorption in AP in vivo. In vitro, MET inhibited RANKL-induced osteoclastogenesis by suppressing the ERK-NFATc1 axis, suggesting a potential mechanism for the anti-bone-resorptive effects of MET in AP.
METHODS: AP was induced in the mandibular first molars of nine 6-week-old male C57BL/6 JJcl mice by pulp exposure for 21 days. MET (50 mg/kg/day) was administered intraperitoneally beginning 1 d before the procedure. Periapical bone resorption was evaluated using micro-computed tomography and tartrate-resistant acid phosphatase (TRAP) staining. In vitro, RAW264.7 murine macrophages were stimulated into osteoclasts using receptor activator of nuclear factor κB ligand (RANKL; 100 ng/mL) for 7 days, whereas the suppressive effect of MET (0.5 mM) on osteoclastogenesis was evaluated using TRAP staining. The mRNA expression of osteoclastogenesis-related genes was measured by real-time quantitative polymerase chain reaction. The effects of MET on extracellular signal-regulated kinase (ERK) and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) signaling were determined using western blotting and luciferase assays, respectively.
RESULTS: MET significantly reduced the lesion size and number of TRAP-positive osteoclasts in vivo at day 21. In vitro, MET significantly inhibited RANKL-induced osteoclastogenesis and decreased the number of TRAP-positive osteoclasts (≥3 nuclei). MET significantly suppressed the RANKL-induced mRNA expression of the osteoclastogenesis-related genes osteoclast-associated receptor, acid phosphatase 5, tartrate resistant, and osteoclast stimulatory transmembrane protein. Moreover, it reduced RANKL-induced p-ERK and NFATc1 signaling.
CONCLUSIONS: MET suppresses bone resorption in AP in vivo. In vitro, MET inhibited RANKL-induced osteoclastogenesis by suppressing the ERK-NFATc1 axis, suggesting a potential mechanism for the anti-bone-resorptive effects of MET in AP.