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Brain-type creatine kinase has a crucial role in osteoclast-mediated bone resorption
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Chang, Eun-Ju | - |
dc.contributor.author | Ha, Jeongim | - |
dc.contributor.author | Oerlemans, Frank | - |
dc.contributor.author | Lee, You Jin | - |
dc.contributor.author | Lee, Soo Woong | - |
dc.contributor.author | Ryu, Jiyoon | - |
dc.contributor.author | Kim, Hyung Joon | - |
dc.contributor.author | Lee, Youngkyun | - |
dc.contributor.author | Kim, Hyun-Man | - |
dc.contributor.author | Choi, Je-Yong | - |
dc.contributor.author | Kim, Jin Young | - |
dc.contributor.author | Shin, Chan Soo | - |
dc.contributor.author | Pak, Youngmi Kim | - |
dc.contributor.author | Tanaka, Sakae | - |
dc.contributor.author | Wieringa, Be | - |
dc.contributor.author | Lee, Zang Hee | - |
dc.contributor.author | Kim, Hong-Hee | - |
dc.date.accessioned | 2010-04-13T04:44:54Z | - |
dc.date.available | 2010-04-13T04:44:54Z | - |
dc.date.issued | 2008-08-30 | - |
dc.identifier.citation | Nat Med. 2008 Sep;14(9):966-72. | en |
dc.identifier.issn | 1546-170X (Electronic) | - |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18724377 | - |
dc.identifier.uri | http://www.nature.com/nm/journal/v14/n9/pdf/nm.1860.pdf | - |
dc.identifier.uri | https://hdl.handle.net/10371/63092 | - |
dc.description.abstract | Osteoclasts differentiate from precursor cells of the monocyte-macrophage lineage and subsequently become activated to be competent for bone resorption through programs primarily governed by receptor activator of nuclear factor-kappaB ligand in cooperation with macrophage colony-stimulating factor. Proteins prominently expressed at late phases of osteoclastogenesis and with a supportive role in osteoclast function are potential therapeutic targets for bone-remodeling disorders. In this study, we used a proteomics approach to show that abundance of the brain-type cytoplasmic creatine kinase (Ckb) is greatly increased during osteoclastogenesis. Decreasing Ckb abundance by RNA interference or blocking its enzymatic activity with a pharmacological inhibitor, cyclocreatine, suppressed the bone-resorbing activity of osteoclasts grown in vitro via combined effects on actin ring formation, RhoA GTPase activity and vacuolar ATPase function. Activities of osteoclasts derived from Ckb-/- mice were similarly affected. In vivo studies showed that Ckb-/- mice were better protected against bone loss induced by ovariectomy, lipopolysaccharide challenge or interleukin-1 treatment than wild-type controls. Furthermore, administration of cyclocreatine or adenoviruses harboring Ckb small hairpin RNA attenuated bone loss in rat and mouse models. Our findings establish an important role for Ckb in the bone-resorbing function of osteoclasts and underscore its potential as a new molecular target for antiresorptive drug development. | en |
dc.language.iso | en | en |
dc.publisher | Nature Publishing Group | en |
dc.subject | Animals | en |
dc.subject | Blotting, Western | en |
dc.subject | Bone Resorption/*enzymology | en |
dc.subject | Creatine Kinase, BB Form/genetics/*metabolism | en |
dc.subject | DNA Primers/genetics | en |
dc.subject | Electrophoresis, Gel, Two-Dimensional | en |
dc.subject | Mice | en |
dc.subject | Mice, Inbred ICR | en |
dc.subject | Mice, Knockout | en |
dc.subject | Osteoclasts/*metabolism | en |
dc.subject | RNA Interference | en |
dc.subject | Reverse Transcriptase Polymerase Chain Reaction | en |
dc.title | Brain-type creatine kinase has a crucial role in osteoclast-mediated bone resorption | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 장은주 | - |
dc.contributor.AlternativeAuthor | 하정민 | - |
dc.contributor.AlternativeAuthor | 이유진 | - |
dc.contributor.AlternativeAuthor | 이수웅 | - |
dc.contributor.AlternativeAuthor | 류지윤 | - |
dc.contributor.AlternativeAuthor | 김형준 | - |
dc.contributor.AlternativeAuthor | 이영균 | - |
dc.contributor.AlternativeAuthor | 김현만 | - |
dc.contributor.AlternativeAuthor | 최제용 | - |
dc.contributor.AlternativeAuthor | 김진영 | - |
dc.contributor.AlternativeAuthor | 신찬수 | - |
dc.contributor.AlternativeAuthor | 박영미 | - |
dc.contributor.AlternativeAuthor | 이장희 | - |
dc.contributor.AlternativeAuthor | 김홍희 | - |
dc.identifier.doi | 10.1038/nm.1860 | - |
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