title: Bromo-honaucin A inhibits osteoclastogenic differentiation in RAW 264.7 cells via Akt and ERK signaling pathways.
abstract: Osteoclasts are unique bone remodeling cells derived from multinucleated myeloid progenitor cells. They play homeostatic vital roles in skeletal modeling and remodeling but also destroy bone masses in many pathological conditions such as osteoporosis and rheumatoid arthritis. Receptor activation of NF-κB ligand (RANKL) is essential to osteoclastogenesis. In this study, we investigated the effects of bromo-honaucin A (Br-H A) isolated from Leptolyngbya crossbyana (cyanobacterium). To investigate the mechanism of the inhibitory effect of Br-H A on osteoclastogenesis, we employed Br-H Ain RANKL-treated murine monocyte/macrophage RAW 264.7 cells for osteoclastic differentiation in-vitro. The inhibitory effects on in-vitro osteoclastogenesis was evaluated by counting the number of Tartarate resistant acid phospatase (TRAP) positive multinucleated cells and by measuring the expression level of osteoclast-specific genes like matrix metalloproteinase 9 (MMP9), cathepsin K (CATH K), GRB2-associated-binding protein 2 (GAB2), c-terminal myc kinase (C-MYC), C-terminal Src kinase (C-SRC) and Microphthalmia-associated transcription factor (MITF). Moreover, Br-H A blocked the resorbing capacity of RAW 264.7 cells on calcium phosphate-coated plates. Finally, Br-H A clearly decreased the expression of Akt and also decreased the activation of ERK. Thus, the study identifies Br-H A as potent inhibitor potentialin the treatment of diseases involving abnormal bone lysis such as osteoporosis, rheumatoid arthritis, and periodontal bone degradation.
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Sapkota
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: School of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 712-74, Republic of Korea.
authors.forename: Hyukjae
authors.initials: H
authors.lastname: Choi
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, CA 92037, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92037, USA. Electronic address: wgerwick@ucsd.edu.
authors.forename: William H
authors.initials: WH
authors.lastname: Gerwick
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, Chonbuk National University, Jeonju 561-756, Republic of Korea. Electronic address: ysoh@jbnu.ac.kr.
authors.forename: Yunjo
authors.initials: Y
authors.lastname: Soh
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003437:Crotonates / Q000737:chemistry* / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D054879:Halogenation; D007527:Isoenzymes / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D053245:RANK Ligand / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D003437:Crotonates; D007527:Isoenzymes; D053245:RANK Ligand; C575082:honaurin A; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D015107:4-Butyrolactone
keywords: Akt; Br-Honaucin A; ERK; Osteoclastogenesis; RANKL; RAW 264.7; p38