title: Inhibitory effects of obovatol on osteoclast differentiation and bone resorption.
abstract: Osteoclasts are polykaryons that have the unique capacity to degrade bone. Modulation of osteoclast formation and function is a promising strategy for the treatment of bone-destructive diseases. Here, we report that obovatol, a natural compound isolated from Magnolia obovata, inhibits receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)-induced osteoclast differentiation in vitro and inflammatory bone loss in vivo. We found that obovatol strongly inhibited osteoclast formation from bone marrow-derived macrophages in a dose-dependent manner without cytotoxicity. Obovatol significantly suppressed RANKL-induced activation of NF-κB, c-Jun-N-terminal kinase, and extracellular signal-regulated kinase signaling pathways. Obovatol also inhibited RANKL-induced expression of the genes c-Fos and nuclear factor of activated T cells c1, which are transcription factors important for osteoclastogenesis. In addition to osteoclast differentiation, obovatol blocked cytoskeletal organization and abrogated the bone resorbing activity of mature osteoclast. Obovatol also accelerated osteoclast apoptosis through the induction of caspase-3 activation. Consistent with its in vitro anti-resorptive effect, obovatol prevented bone loss induced by lipopolysaccharide in vivo. Together, our data suggest that obovatol may be a useful therapeutic agent for the treatment of pathological bone disorders characterized by excessive osteoclastic bone resorption.
authors: Skeletal Diseases Genome Research Center, Kyungpook National University and Hospital, Daegu 700-412, Republic of Korea. Electronic address: biohjk@hanmail.net.
authors: Hyun-Ju
authors: HJ
authors: Kim
authors: Skeletal Diseases Genome Research Center, Kyungpook National University and Hospital, Daegu 700-412, Republic of Korea.
authors: Jung Min
authors: JM
authors: Hong
authors: Skeletal Diseases Genome Research Center, Kyungpook National University and Hospital, Daegu 700-412, Republic of Korea.
authors: Hye-Jin
authors: HJ
authors: Yoon
authors: Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, Daejon 305-600, Republic of Korea.
authors: Byoung-Mog
authors: BM
authors: Kwon
authors: Department of Biochemistry and Cell Biology, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
authors: Je-Yong
authors: JY
authors: Choi
authors: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
authors: In-Kyu
authors: IK
authors: Lee
authors: Skeletal Diseases Genome Research Center, Kyungpook National University and Hospital, Daegu 700-412, Republic of Korea; Department of Orthopedic Surgery, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea. Electronic address: syukim@knu.ac.kr.
authors: Shin-Yoon
authors: SY
authors: Kim
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001862:Bone Resorption / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy*; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D010647:Phenyl Ethers / Q000494:pharmacology* / Q000627:therapeutic use*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D053245:RANK Ligand / Q000494:pharmacology; D011859:Radiography
chemical_list: D001713:Biphenyl Compounds; D050071:Bone Density Conservation Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D010647:Phenyl Ethers; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; C036795:obovatol; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3
keywords: Apoptosis; Bone resorption; Cytoskeletal organization; Obovatol; Osteoclast; RANKL