title: Biselyngbyaside, isolated from marine cyanobacteria, inhibits osteoclastogenesis and induces apoptosis in mature osteoclasts.
abstract: The mass and function of bones depend on the maintenance of a complicated balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. An inhibitor of osteoclast differentiation and/or function is expected to be useful for treatment of bone lytic diseases such as osteoporosis, rheumatoid arthritis, and tumor metastasis into bone. Biselyngbyaside is a recently isolated macrolide compound from marine cyanobacteria Lyngbya sp. that shows wide-spectrum cytotoxicity toward human tumor cell lines. In this study, we investigated the effects of biselyngbyaside on osteoclast differentiation and function. Biselyngbyaside inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in mouse monocytic RAW264 cells and primary bone marrow-derived macrophages at a low concentration. Similarly, biselyngbyaside suppressed osteoblastic cell-mediated osteoclast differentiation in cocultures. In the RANKL-induced signaling pathway, biselyngbyaside inhibited the expression of c-Fos and NFATc1, which are important transcription factors in osteoclast differentiation. In mature osteoclasts, biselyngbyaside decreased resorption-pit formation. Biselyngbyaside also induced apoptosis accompanied by the induction of caspase-3 activation and nuclear condensation, and these effects were negated by the pancaspase inhibitor z-VAD-FMK. Taken together, the present findings indicate that biselyngbyaside suppresses bone resorption via inhibition of osteoclastogenesis and induction of apoptosis. Thus, biselyngbyaside may be useful for the prevention of bone lytic diseases.
authors.affiliation: Department of Nutriproteomics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yonezawa
authors.forename: Naomi
authors.initials: N
authors.lastname: Mase
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Teruya
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Byung-Yoon
authors.initials: BY
authors.lastname: Cha
authors.forename: Kazumi
authors.initials: K
authors.lastname: Yagasaki
authors.forename: Kiyotake
authors.initials: K
authors.lastname: Suenaga
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nagai
authors.forename: Je-Tae
authors.initials: JT
authors.lastname: Woo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003034:Coated Pits, Cell-Membrane / Q000187:drug effects / Q000378:metabolism; D018920:Coculture Techniques; D006801:Humans; D018942:Macrolides / Q000302:isolation & purification / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D054300:Oscillatoria / Q000737:chemistry*; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000494:pharmacology; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D018942:Macrolides; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; C505688:TNFSF11 protein, human; C541338:biselyngbyaside; D020928:Mitogen-Activated Protein Kinases; D025262:Vacuolar Proton-Translocating ATPases