Seok Jiwon, Kim Myoung Ok, Kim Sung-Hyun, Ryu Ka-Young, Kim Jae-Young, Lee Heon-Jin, Kim Yong-Gun, Lee Youngkyun
Department of Biochemistry, School of Dentistry, Kyungpook National University, Daegu, South Korea.
Department of Animal Biotechnology, College of Ecology and Environmental Science, Kyungpook National University, Sangju, South Korea.
J Periodontol. 2025 Feb;96(2):164-175. doi: 10.1002/JPER.23-0541. Epub 2024 Jun 20.
Bacterial-induced inflammation instigates the destruction of hard and soft tissues surrounding teeth in periodontitis. In severe cases, the increased number and activity of osteoclasts induces the resorption of alveolar bones, ultimately leading to tooth loss. Because of their diverse chemical structures and bioactivities, natural compounds are often suggested to treat a wide variety of diseases, including inflammatory disorders.
In the present study, we demonstrated an inhibitory effect of gossypetin, a hexahydroxy flavone, on osteoclast differentiation and bone resorption using in vitro culture of osteoclasts from mouse bone marrow macrophage (BMM) precursors and in vivo model of ligature-induced periodontitis in mice.
Gossypetin significantly reduced the differentiation of osteoclasts from mouse BMM precursors in the presence of the receptor activator of nuclear factor κB ligand (RANKL). In vitro, gossypetin inhibited critical signaling events downstream of RANKL including the auto-amplification of nuclear factor of activated T-cells, cytoplasmic 1, Ca oscillations, and the generation of reactive oxygen species. In a mouse ligature-induced periodontitis model, the administration of gossypetin significantly reduced osteoclastogenesis and alveolar bone resorption. Furthermore, gossypetin prevented the ligature-induced increase in macrophages and T cells and reduced the production of tumor necrosis factor-α and interleukin-6.
Taken together, these results show anti-osteoclastogenic and anti-inflammatory effects of gossypetin, suggesting the potential use of this natural compound in periodontitis.
细菌诱导的炎症会引发牙周炎中牙齿周围软硬组织的破坏。在严重情况下，破骨细胞数量增加及活性增强会导致牙槽骨吸收，最终导致牙齿脱落。由于天然化合物具有多样的化学结构和生物活性，常被建议用于治疗包括炎症性疾病在内的多种疾病。
在本研究中，我们使用从小鼠骨髓巨噬细胞（BMM）前体细胞体外培养破骨细胞以及小鼠结扎诱导性牙周炎体内模型，证明了六羟基黄酮棉皮素对破骨细胞分化和骨吸收具有抑制作用。
在存在核因子κB配体受体激活剂（RANKL）的情况下，棉皮素显著降低了小鼠BMM前体细胞向破骨细胞的分化。在体外，棉皮素抑制了RANKL下游的关键信号事件，包括活化T细胞核因子细胞质1的自扩增、Ca振荡以及活性氧的产生。在小鼠结扎诱导性牙周炎模型中，给予棉皮素显著减少了破骨细胞生成和牙槽骨吸收。此外，棉皮素可防止结扎诱导的巨噬细胞和T细胞增加，并减少肿瘤坏死因子-α和白细胞介素-6的产生。
综上所述，这些结果表明棉皮素具有抗破骨细胞生成和抗炎作用，提示这种天然化合物在牙周炎治疗中具有潜在用途。
