Department of Oral Biochemistry, School of Dentistry, Dankook University, Anseo-dong, Cheonan, Choongnam, Republic of Korea.
Arch Oral Biol. 2012 Dec;57(12):1623-32. doi: 10.1016/j.archoralbio.2012.06.012. Epub 2012 Jul 12.
Periodontitis is an inflammatory disease that affects connective tissue attachments and the supporting bone that surrounds the teeth. Gingival fibroblasts induce the overexpression of matrix metalloproteinase (MMP), which is involved in inflammatory progression in periodontitis. Osteoclasts are responsible for skeletal modeling and remodeling but may also destroy bone in several bone diseases, including osteoporosis and periodontitis. This study examined the anti-destructive effects of myricetin on human gingival fibroblasts (HGF) under lipopolysaccharide- (LPS-) induced inflammatory conditions, and the anti-osteoclastogenetic effect of myricetin on the receptor activator of NF-κB ligand (RANKL) induced RAW264.7 cells was also investigated.
The effects of myricetin on HGF were determined by measuring the cell viability and mRNA expression and enzyme activity of tissue-destructive proteins, including MMP-1, MMP-2 and MMP-8. The effects of myricetin on osteoclasts were examined by measuring the following: (1) the cell viability, (2) the formation of tartrate-resistant acid phosphatase (TRAP)(+) multinucleated cells, (3) MAPK signalling pathways (4) mRNA expression of osteoclast-associated genes and (5) tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) secretion.
The myricetin had no effects on the cell viability of the HGF and decreased the mRNA expression and enzyme activity of MMP-1, MMP-2 and MMP-8 in the HGF. Myricetin inhibited the formation of RANKL-stimulated TRAP(+) multinucleated cells. Myricetin also inhibited the RANKL-stimulated activation of p-38, ERK and cSrc signaling, and inhibited the RANKL-stimulated degradation of I(k)B in the RAW264.7 cells. In addition, the RANKL-stimulated induction of NFATc1 transcription factors was abrogated by myricetin. Myricetin decreased the mRNA expression of osteoclast-associated genes, including cFOS, TRAP and cathepsin K in the RAW264.7 cells. Myricetin inhibited the secretion of LPS-induced TNF-α and IL-1β in the RAW264.7 cells.
These findings suggest that myricetin has therapeutic effects on bone-destructive processes, such as those that occur in periodontal diseases.
牙周炎是一种影响连接组织附着和牙齿周围支撑骨的炎症性疾病。牙龈成纤维细胞诱导基质金属蛋白酶（MMP）的过度表达，该酶参与牙周炎的炎症进展。破骨细胞负责骨骼建模和重塑，但也可能破坏包括骨质疏松症和牙周炎在内的几种骨骼疾病中的骨骼。本研究探讨了杨梅素在脂多糖（LPS）诱导的炎症条件下对人牙龈成纤维细胞（HGF）的抗破坏作用，以及杨梅素对核因子-κB 配体（RANKL）诱导的 RAW264.7 细胞的抗破骨细胞生成作用。
通过测量组织破坏性蛋白（包括 MMP-1、MMP-2 和 MMP-8）的细胞活力和 mRNA 表达及酶活性来确定杨梅素对 HGF 的影响。通过测量以下内容来检查杨梅素对破骨细胞的影响：（1）细胞活力，（2）抗酒石酸酸性磷酸酶（TRAP）（+）多核细胞的形成，（3）MAPK 信号通路，（4）破骨细胞相关基因的 mRNA 表达和（5）肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的分泌。
杨梅素对 HGF 的细胞活力没有影响，但降低了 HGF 中 MMP-1、MMP-2 和 MMP-8 的 mRNA 表达和酶活性。杨梅素抑制了 RANKL 刺激的 TRAP（+）多核细胞的形成。杨梅素还抑制了 RANKL 刺激的 p-38、ERK 和 cSrc 信号的激活，并抑制了 RANKL 刺激的 RAW264.7 细胞中 I（k）B 的降解。此外，杨梅素阻断了 RANKL 刺激的 NFATc1 转录因子的诱导。杨梅素降低了 RAW264.7 细胞中破骨细胞相关基因（包括 cFOS、TRAP 和组织蛋白酶 K）的 mRNA 表达。杨梅素抑制了 LPS 诱导的 RAW264.7 细胞中 TNF-α和 IL-1β的分泌。
这些发现表明，杨梅素对骨破坏过程具有治疗作用，例如牙周病中发生的骨破坏过程。
