Bavachalcone inhibits osteoclast differentiation through suppression of NFATc1 induction by RANKL.
Osteoclasts are cells that have a specialized role for bone resorption and are responsible for many bone diseases such as osteoporosis. As herbal products are invaluable sources in discovery of compounds for new therapies, we sought to identify compounds efficacious in suppressing osteoclastogenesis from medicinal plants that have been implicated for treatment of osteoporotic conditions. Bavachalcone was isolated from Psoralea corylifolia, and its effects on osteoclast differentiation were evaluated with primary cultures of osteoclast precursor cells. In addition, the molecular mechanism of action was investigated. Bavachalcone inhibited osteoclast formation from precursor cells with the IC(50) of approximately 1.5 microg ml(-1). The activation of MEK, ERK, and Akt by receptor activator of nuclear factor kappaB ligand (RANKL), the osteoclast differentiation factor, was prominently reduced in the presence of bavachalcone. The induction of c-Fos and NFATc1, key transcription factors for osteoclastogenesis, by RANKL was also suppressed by bavachalcone. In conclusion, bavachalcone inhibits osteoclastogenesis by interfering with the ERK and Akt signaling pathways and the induction of c-Fos and NFATc1 during differentiation. Our results suggest that bavachalcone may be useful as a therapeutic drug for bone resorption-associated diseases.
Park
Cheol Kyu
CK
Department of Cell and Developmental Biology, BK21 Program, Dental Research Institute, Seoul National University School of Dentistry, 28 Yeongon-Dong, Chongno-Gu, Seoul 110-749, Republic of Korea.
Lee
Youngkyun
Y
Chang
Eun-Ju
EJ
Lee
Ming Hong
MH
Yoon
Jeong Hoon
JH
Ryu
Jae-Ha
JH
Kim
Hong-Hee
HH
D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy; D002454:Cell Differentiation / Q000187:drug effects; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000235:genetics / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D050778:NFATC Transcription Factors / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D029907:Psoralea / Q000737:chemistry; D053245:RANK Ligand / Q000378:metabolism*
D047188:Chalcones; D047309:Flavones; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; C508227:bavachalcone; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases