A novel benzamide derivative protects ligature-induced alveolar bone erosion by inhibiting NFATc1-mediated osteoclastogenesis

作者：Ihn Hye Jung; Lee Taeho; Lee Doohyun; Kim Ju Ang; Kim Kiryeong; Lim Soomin; Kim Jae Young; Lee Youngkyun; Kim Sang Hyun; Lee Hyun Shik; Shin Hong In; Park Eui Kyun^*

来源：Toxicology and Applied Pharmacology, 2018, 355: 9-17.

DOI：10.1016/j.taap.2018.06.017

• Benzamide
• OCLI-070
• Osteoclast
• Bone resorption
• Alveolar bone loss

Since elevated osteoclast formation and/or activity by inhibitory responses against pathogens leads to diverse osteolytic bone diseases including periodontitis, inhibition of osteoclast differentiation and bone resorption has been a primary therapeutic strategy. In this study, we investigated the therapeutic potential of a novel benzamide-linked molecule, OCLI-070, for preventing alveolar bone loss in mice with ligature-induced experimental periodontitis. OCLI-070 inhibited osteoclast formation by acting on both early and late stages of differentiation, and attenuated the induction of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and the expression of osteoclast-specific genes. In addition, OCLI-070 significantly suppressed the formation of actin rings and resorption pits. Analysis of the inhibitory action of OCLI-070 showed that it markedly suppressed receptor activator of nuclear factor-kappa B ligand (RANKL)-induced extracellular signal-regulated kinase (ERK) and NF-kappa B signaling cascades. Moreover, OCLI-070 prevented ligature-induced alveolar bone erosion in mice by suppressing osteoclast formation. These findings demonstrate that OCLI-070 attenuated osteoclast differentiation and function as well as ligature-induced bone erosion by inhibiting RANKL-mediated ERK and NF-kappa B signaling pathways.

• 出版日期2018-9-15