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rdf:type |
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lifeskim:mentions |
umls-concept:C0029433,
umls-concept:C0031928,
umls-concept:C0389995,
umls-concept:C0527443,
umls-concept:C0574895,
umls-concept:C0871261,
umls-concept:C1171350,
umls-concept:C1335631,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C1948023,
umls-concept:C2911692
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pubmed:issue |
12
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pubmed:dateCreated |
2009-11-5
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pubmed:abstractText |
The small GTPase Rho and Rho-associated protein kinase (Rho kinase, ROCK) signal participates in a variety of biological functions including vascular contraction, tumor invasion, and penile erection. Evidence also suggests Rho-ROCK is involved in signaling for mesenchymal cellular differentiation. However, whether it is involved in osteoblastic differentiation is unknown. We therefore asked whether Rho-ROCK signaling participates in recombinant human bone morphogenetic protein (rhBMP-2)-induced osteogenesis both in vitro and in vivo. Continuous delivery of a specific ROCK inhibitor (Y-27632) enhanced ectopic bone formation induced by rhBMP-2 impregnated into an atelocollagen carrier in mice without affecting systemic bone metabolism. Treatment with Y-27632 also enhanced the osteoblastic differentiation of cultured murine neonatal calvarial cells. These effects were associated with increased expression of BMP-4 gene. Expression of a dominant negative mutant of ROCK in ST2 cells promoted osteoblastic differentiation, while a constitutively active mutant of ROCK attenuated osteoblastic differentiation and the ROCK inhibitor reversed this phenotype. Thus, ROCK inhibits osteogenesis, and a ROCK inhibitor in combination with the local delivery of rhBMP/collagen composite may be clinically applicable for stimulating bone formation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amides,
http://linkedlifedata.com/resource/pubmed/chemical/BMP2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bmp4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 2,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 4,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen,
http://linkedlifedata.com/resource/pubmed/chemical/Drug Carriers,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Y 27632,
http://linkedlifedata.com/resource/pubmed/chemical/atelocollagen,
http://linkedlifedata.com/resource/pubmed/chemical/rho-Associated Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1528-1132
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
467
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3087-95
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pubmed:dateRevised |
2011-3-3
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pubmed:meshHeading |
pubmed-meshheading:19609629-Amides,
pubmed-meshheading:19609629-Animals,
pubmed-meshheading:19609629-Animals, Newborn,
pubmed-meshheading:19609629-Bone Morphogenetic Protein 2,
pubmed-meshheading:19609629-Bone Morphogenetic Protein 4,
pubmed-meshheading:19609629-Cell Differentiation,
pubmed-meshheading:19609629-Cell Movement,
pubmed-meshheading:19609629-Cells, Cultured,
pubmed-meshheading:19609629-Collagen,
pubmed-meshheading:19609629-Dose-Response Relationship, Drug,
pubmed-meshheading:19609629-Drug Carriers,
pubmed-meshheading:19609629-Humans,
pubmed-meshheading:19609629-Male,
pubmed-meshheading:19609629-Mice,
pubmed-meshheading:19609629-Mice, Inbred ICR,
pubmed-meshheading:19609629-Mutation,
pubmed-meshheading:19609629-Ossification, Heterotopic,
pubmed-meshheading:19609629-Osteoblasts,
pubmed-meshheading:19609629-Osteogenesis,
pubmed-meshheading:19609629-Pilot Projects,
pubmed-meshheading:19609629-Protein Kinase Inhibitors,
pubmed-meshheading:19609629-Pyridines,
pubmed-meshheading:19609629-RNA, Messenger,
pubmed-meshheading:19609629-Recombinant Proteins,
pubmed-meshheading:19609629-Skull,
pubmed-meshheading:19609629-Stromal Cells,
pubmed-meshheading:19609629-Transfection,
pubmed-meshheading:19609629-rho-Associated Kinases
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pubmed:year |
2009
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pubmed:articleTitle |
Stimulation of ectopic bone formation in response to BMP-2 by Rho kinase inhibitor: a pilot study.
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pubmed:affiliation |
Department of Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-2 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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