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Toxicol Appl Pharmacol. 2018 Sep 15;355:9-17. doi: 10.1016/j.taap.2018.06.017. Epub 2018 Jun 20.

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

Author information

1
Institute for Hard Tissue and Bio-tooth Regeneration, Kyungpook National University, Daegu 41940, Republic of Korea.
2
College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea.
3
Department of Oral Pathology and Regenerative Medicine, School of Dentistry, IHBR, Kyungpook National University, Daegu 41940, Republic of Korea.
4
Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu 41940, Republic of Korea.
5
Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
6
School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of Korea.
7
Department of Oral Pathology and Regenerative Medicine, School of Dentistry, IHBR, Kyungpook National University, Daegu 41940, Republic of Korea. Electronic address: epark@knu.ac.kr.

Abstract

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-κB ligand (RANKL)-induced extracellular signal-regulated kinase (ERK) and NF-κB 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-κB signaling pathways.

KEYWORDS:

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

PMID:
29935282
DOI:
10.1016/j.taap.2018.06.017
[Indexed for MEDLINE]

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