The novel isoflavone derivatives inhibit RANKL-induced osteoclast formation.
Isoflavones are compounds structurally similar to the mammalian estrogens and have received considerable attention for their preventive actions on bone loss. Here, we synthesized the novel isoflavone derivatives and examined their activities in bone cells. We found that the novel isoflavone derivatives markedly inhibited the receptor activator of nuclear factor kappa B ligand (RANKL) plus macrophage colony stimulating factor (M-CSF)-induced osteoclastic differentiation from bone marrow stromal cells and RAW264.7 macrophage cells. Treatment of RAW264.7 macrophages with RANKL-induced extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK) phosphorylation. However, RANKL-induced p38 and JNK but not ERK phosphorylation was attenuated by isoflavone derivatives. Furthermore, RANKL-mediated increase of p65 phosphorylation at Ser⁵³⁶, NF-κB-specific DNA-protein complex formation and κB-luciferase activity was inhibited by isoflavone derivatives. On the other hand, isoflavone derivatives did not affect the cell proliferation and differentiation of human cultured osteoblasts. Our data suggest that the novel isoflavone derivatives inhibit osteoclastogenesis from bone marrow stromal cells and macrophage cells via attenuation of RANKL-induced p38, JNK and NF-κB activation.
Tang
Chih-Hsin
CH
Department of Pharmacology, School of Medicine, China Medical University and Hospital, Taichung, Taiwan. chtang@mail.cmu.edu.tw
Chang
Chih-Shiang
CS
Tan
Tzu-Wei
TW
Liu
Shan-Chi
SC
Liu
Ju-Fang
JF
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001862:Bone Resorption / Q000517:prevention & control; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D007529:Isoflavones / Q000737:chemistry* / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D007529:Isoflavones; D016328:NF-kappa B; D053245:RANK Ligand; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases