DC Field | Value | Language |
---|---|---|
dc.contributor.author | Jeong, Byung-Chul | ko |
dc.contributor.author | Kim, Hyun-Joo | ko |
dc.contributor.author | Bae, In-Ho | ko |
dc.contributor.author | Lee, Kkot-Nim | ko |
dc.contributor.author | Lee, Kwang-Youl | ko |
dc.contributor.author | Oh, Won-Mann | ko |
dc.contributor.author | Kim, Sun-Hun | ko |
dc.contributor.author | Kang, In-Chol | ko |
dc.contributor.author | Lee, Shee-Eun | ko |
dc.contributor.author | Koh, Gou Young | ko |
dc.contributor.author | Kim, Kyung-Keun | ko |
dc.contributor.author | Koh, Jeong-Tae | ko |
dc.date.accessioned | 2013-03-12T04:33:51Z | - |
dc.date.available | 2013-03-12T04:33:51Z | - |
dc.date.created | 2012-02-06 | - |
dc.date.created | 2012-02-06 | - |
dc.date.issued | 2010-02 | - |
dc.identifier.citation | BONE, v.46, no.2, pp.479 - 486 | - |
dc.identifier.issn | 8756-3282 | - |
dc.identifier.uri | http://hdl.handle.net/10203/101344 | - |
dc.description.abstract | Introduction: Angiogenesis is closely associated with bone formation, especially endochondral ossification. Angiopoietin 1 (Ang1) is a specific growth factor functioning to generate a stable and matured vasculature through the Tie2 receptor/PI3K/AKT pathway. Recently cartilage oligomeric matrix protein (COMP)-Ang1, an Ang1 variant which is more potent than native Ang1 in phosphorylating Tie2 receptor and AKT, was developed. This study was designed to examine the effects of angiogenic COMP-Ang1 on BMP2-induced osteoblast differentiation and bone formation. Methods: Expression of endogenous Ang-1 and its binding receptor Tie 2 mRNA was examined in osteoblast-like cells and primary mouse calvarial cells by RT-PCR analysis, and was also monitored during osteoblast differentiation induced by BMP-2 and/or ascorbic acid and beta-glycerophosphate. Effects of COMP-Ang-1 on osteoblast differentiation and mineralization were evaluated by alkaline phosphatase (ALP) activity and osteocalcin (OC) production, and Alizarin red stain. For a molecular mechanism, Western blot and OG2 and 6xOSE promoter assays were done. For in vivo evaluation, adenoviral (Ad) vectors containing COMP-Ang-1 or BMP-2 gene were administered into thigh muscle of mice, and after 2 weeks bone formation was analyzed by micro-computed tomography and histology. Angiogenic event of COMP-Ang1 was confirmed by immunofluorescence analysis with anti-CD31 antibody. Results: Expression of Tie2 receptor was significantly increased in the course of osteoblast differentiation. Treatment or overexpression of COMP-Ang1 enhanced BMP2-induced ALP activity, OC production, and mineral deposition in a dose-dependent manner. In addition, COMP-Ang1 synergistically increased OG2 and 6xOSE promoter activities of BMP2, and sustained p38, Smad and AKT phosphorylation of BMP2. Notably, in vivo intramuscular injection of COMP-Ang1 dose-dependently enhanced BMP2-induced ectopic bone formation with increases in CD31 reactivity. Conclusions: These results suggest that COMP-Ang1 synergistically enhanced osteoblast differentiation and bone formation through potentiating BMP2 signaling pathways and angiogenesis. Combination of BMP2 and COMP-Ang1 should be clinically useful for therapeutic application to fracture and destructive bone diseases. (C) 2009 Elsevier Inc. All rights reserved. | - |
dc.language | English | - |
dc.publisher | Elsevier Science Inc | - |
dc.subject | GENE-THERAPY | - |
dc.subject | POSTNATAL NEOVASCULARIZATION | - |
dc.subject | MORPHOGENETIC PROTEINS | - |
dc.subject | SIGNAL-TRANSDUCTION | - |
dc.subject | ANGIOGENESIS | - |
dc.subject | VEGF | - |
dc.subject | KINASE | - |
dc.subject | EXPRESSION | - |
dc.subject | PATHWAY | - |
dc.subject | BMP-2 | - |
dc.title | COMP-Ang1, a chimeric form of Angiopoietin 1, enhances BMP2-induced osteoblast differentiation and bone formation | - |
dc.type | Article | - |
dc.identifier.wosid | 000274702800033 | - |
dc.identifier.scopusid | 2-s2.0-74249106462 | - |
dc.type.rims | ART | - |
dc.citation.volume | 46 | - |
dc.citation.issue | 2 | - |
dc.citation.beginningpage | 479 | - |
dc.citation.endingpage | 486 | - |
dc.citation.publicationname | BONE | - |
dc.identifier.doi | 10.1016/j.bone.2009.09.019 | - |
dc.contributor.localauthor | Koh, Gou Young | - |
dc.contributor.nonIdAuthor | Jeong, Byung-Chul | - |
dc.contributor.nonIdAuthor | Kim, Hyun-Joo | - |
dc.contributor.nonIdAuthor | Bae, In-Ho | - |
dc.contributor.nonIdAuthor | Lee, Kkot-Nim | - |
dc.contributor.nonIdAuthor | Lee, Kwang-Youl | - |
dc.contributor.nonIdAuthor | Oh, Won-Mann | - |
dc.contributor.nonIdAuthor | Kim, Sun-Hun | - |
dc.contributor.nonIdAuthor | Kang, In-Chol | - |
dc.contributor.nonIdAuthor | Lee, Shee-Eun | - |
dc.contributor.nonIdAuthor | Kim, Kyung-Keun | - |
dc.contributor.nonIdAuthor | Koh, Jeong-Tae | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | COMP-Ang1 | - |
dc.subject.keywordAuthor | Tie2 | - |
dc.subject.keywordAuthor | Bone morphogenetic protein | - |
dc.subject.keywordAuthor | Bone formation | - |
dc.subject.keywordAuthor | Angiogenesis | - |
dc.subject.keywordPlus | GENE-THERAPY | - |
dc.subject.keywordPlus | POSTNATAL NEOVASCULARIZATION | - |
dc.subject.keywordPlus | MORPHOGENETIC PROTEINS | - |
dc.subject.keywordPlus | SIGNAL-TRANSDUCTION | - |
dc.subject.keywordPlus | ANGIOGENESIS | - |
dc.subject.keywordPlus | VEGF | - |
dc.subject.keywordPlus | KINASE | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.subject.keywordPlus | BMP-2 | - |
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