title: OA-4 inhibits osteoclast formation and bone resorption via suppressing RANKL induced P38 signaling pathway.
abstract: Osteoclasts are one of the key therapeutic targets for a variety of orthopedic diseases such as osteoporosis and osteoarthritis. In this study, we synthesized a novel compound N-(3-(cyclohexylcarbamoyl) phenyl)-1H-indole-2- carboxamide (termed as OA-4) and investigated the effects of OA-4 on the differentiation and function of osteoclasts. OA-4 markedly diminished osteoclast differentiation and osteoclast specific gene expression in a dose-dependent manner. In addition, OA-4 dose-dependently suppressed osteoclastic bone resorption. Furthermore, we found OA-4 attenuated RANKL-induced p38 phosphorylation without affecting JNK or NF-κB signaling pathways. Collectively, we synthesized a novel compound OA-4 which can inhibit osteoclast formation and functions via the suppression of p38 signaling pathway.
authors.forename: B
authors.initials: B
authors.lastname: Tian
authors.forename: A
authors.initials: A
authors.lastname: Qin
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Shao
authors.forename: T
authors.initials: T
authors.lastname: Jiang
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Zhai
authors.forename: H W
authors.initials: HW
authors.lastname: Li
authors.forename: T T
authors.initials: TT
authors.lastname: Tang
authors.forename: Q
authors.initials: Q
authors.lastname: Jiang
authors.forename: K R
authors.initials: KR
authors.lastname: Dai
authors.forename: M H
authors.initials: MH
authors.lastname: Zheng
authors.forename: Y P
authors.initials: YP
authors.lastname: Yu
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, The People's Republic of China, Address: 639 Zhizaoju Road, Shanghai 200011, P.R.China. zhuzhe-nan2006@126.com.
authors.forename: Z A
authors.initials: ZA
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D001857:Bone Matrix / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D053245:RANK Ligand / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D001549:Benzamides; D007211:Indoles; C000591020:N-(3-(cyclohexylcarbamoyl)phenyl)-1H-indole-2-carboxamide; D053245:RANK Ligand; D048051:p38 Mitogen-Activated Protein Kinases