title: Silk fibroin hydrolysate inhibits osteoclastogenesis and induces apoptosis             of osteoclasts derived from RAW 264.7 cells.
abstract: Bone disease can be associated with bone resorption by osteoclasts, and interest in the development of antiresorptive agents has recently increased. The hydrolysate of silk fibroin has been studied with respect to such biomedical applications. In a previous study, silk fibroin showed indirect inhibitory effects on the differentiation of osteoclasts. To further evaluate the effect of a hydrolysate of silk fibroin on osteoclasts, we investigated the direct effects of the silk fibroin hydrolysate on osteoclastogenesis and apoptosis of osteoclasts induced by receptor activation of nuclear factor κB ligand (RANKL). The silk fibroin hydrolysate inhibited RANKL-induced formation of tartrate-resistant acid phosphatase (TRAP) in RAW 264.7 cells. The inhibitory effect of the silk fibroin hydrolysate resulted in the decreased expression of osteoclast marker genes, such as matrix metalloproteinase-9 (MMP-9), cathepsin-K and calcitonin receptor (CTR). In addition, the silk fibroin hydrolysate blocked the signaling pathways of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) and expression of transcription factors, such as nuclear factor of activated T cells c1 (NFATc1) and NF-κB. Finally, the silk fibroin hydrolysate induced apoptosis signaling cascades. Taken together, the present results indicate that silk fibroin hydrolysate has antiresorptive activity by both inhibiting osteoclastogenesis and inducing osteoclast apoptosis.
authors.affiliation: Sericultural and Apicultural Materials Division, National Academy                     of Agricultural Science, RDA, Suwon 441-100, Republic of Korea.
authors.forename: Jeon-Woo
authors.initials: JW
authors.lastname: Chon
authors.forename: Hyeryeon
authors.initials: H
authors.lastname: Kim
authors.forename: Ha-Na
authors.initials: HN
authors.lastname: Jeon
authors.forename: Kyungho
authors.initials: K
authors.lastname: Park
authors.forename: Kwang-Gill
authors.initials: KG
authors.lastname: Lee
authors.forename: Joo-Hong
authors.initials: JH
authors.lastname: Yeo
authors.forename: Haeyong
authors.initials: H
authors.lastname: Kweon
authors.forename: Heui-Sam
authors.initials: HS
authors.lastname: Lee
authors.forename: You-Young
authors.initials: YY
authors.lastname: Jo
authors.forename: Yoo Kyoung
authors.initials: YK
authors.lastname: Park
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D056657:Cathepsin K / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005349:Fibroins / Q000494:pharmacology*; D051550:I-kappa B Kinase / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D010010:Osteoclasts / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology*; D018003:Receptors, Calcitonin / Q000378:metabolism; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D010446:Peptide Fragments; D018003:Receptors, Calcitonin; C498144:Rela protein, mouse; D048029:TNF Receptor-Associated Factor 6; D051996:Transcription Factor RelA; D005349:Fibroins; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K; C534132:Ctsk protein, mouse; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat