ISSN 2052-1219 (online)

Bone Abstracts (2013) 1 PP418 | DOI: 10.1530/boneabs.1.PP418

Myricetin suppress LPS-induced MMP expression in human periodontal ligament fibroblasts and inhibit osteoclastogenesis by downregulating NFATc1 in LPS-induced RAW 264.7 cells

Seon-Yle Ko & Young-Joo Jang

Dankook University, Cheonan, Republic of Korea.

Periodontitis is an inflammatory disease that affects connective tissue attachments and the supporting bone that surrounds the teeth. Periodontal ligament 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 periodontal ligament fibroblasts (PDLF) under lipopolysaccharide LPS- induced inflammatory conditions, and the anti-osteoclastogenetic effect of myricetin on the LPS-induced RAW264.7 cells was also investigated. The effects of myricetin on PDLF were determined by measuring the cell viability and mRNA expression and enzyme activity of tissue-destructive proteins, including MMP-1, MMP-2, and MMP-3. The effects of myricetin on osteoclasts were examined by measuring the following: i) the cell viability, ii) the formation of tartrate-resistant acid phosphatase (TRAP+) multinucleated cells, iii) MAPK signaling pathways, iv) mRNA expression of osteoclast-associated genes, v) nitric oxide (NO) and interleukin 6 (IL6) secretion and vi) mRNA expression and enzyme activity of MMP-8. The myricetin had no effects on the cell viability of the PDLF and decreased the mRNA expression and enzyme activity of MMP-2 and MMP-3 in the PDLF. Myricetin inhibited the formation of LPS-stimulated TRAP(+) multinucleated cells. Myricetin also inhibited the LPS-stimulated activation of ERK signaling in the RAW264.7 cells. The LPS-stimulated induction of NFATc1 transcription factors was abrogated by myricetin. Myricetin decreased the mRNA expression of osteoclast-associated genes, including TRAP and cathepsin K in the RAW264.7 cells. Myricetin inhibited the secretion of LPS-induced NO and IL6 in the RAW264.7 cells. In addition, myricetin decreased the mRNA expression and enzyme activity of MMP-8 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.

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