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Biselyngbyaside, isolated from marine cyanobacteria, inhibits osteoclastogenesis and induces apoptosis in mature osteoclasts
Author(s) -
Yonezawa Takayuki,
Mase Naomi,
Sasaki Hiroaki,
Teruya Toshiaki,
Hasegawa Shinichi,
Cha ByungYoon,
Yagasaki Kazumi,
Suenaga Kiyotake,
Nagai Kazuo,
Woo JeTae
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23213
Subject(s) - osteoclast , rankl , bone resorption , osteoblast , apoptosis , chemistry , microbiology and biotechnology , cancer research , receptor , endocrinology , activator (genetics) , biology , biochemistry , in vitro
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. J. Cell. Biochem. 113: 440–448, 2012. © 2011 Wiley Periodicals, Inc.