Linked Life Data

17559111

Source:http://linkedlifedata.com/resource/pubmed/id/17559111

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-11-5
pubmed:abstractText
C3H10T1/2/Osx, a stably transfected cell line with Osterix (Osx), was produced and chondrocytic and osteoblastic differentiation were studied in vitro. Osx promoted osteoblastic lineage that was dexamethasone dependent. Furthermore, in vivo, Osx induced ectopic mineralization in a heterotopic mouse muscle model. Skeletogenesis involves a cascade of molecular activities sequentially performed by osteoblasts and chondroblasts. A transcriptional factor gene Osx appears to influence cell disposition toward the chondrocytic or osteoblastic phenotype and therefore may be an important signaling cue for bone formation. Understanding the molecular conditions involved with Osx promoted osteoblast differentiation will facilitate therapeutic applications of Osx. Consequently, the objective of this study was to investigate chondrocytic and osteoblastic phenotype differentiation using an Osx plasmid DNA exploiting both in vitro and in vivo methodologies. In vitro, a stably transfected C3H10T1/2/Osx cell line was established and promotion of either an osteoblast or chondroblast phenotype was performed by selectively introducing dexamethasone (dex) and assaying mRNA content and phenotype markers. In vivo, a mouse muscle model was used to determine heterotopic ossification using designated Osx plasmid DNA doses incorporated in a (50:50 Poly (D,L-lactide-co-glycolide) (i.e., PLGA) 3D scaffold. Histological assessment was used to determine implant responses. Quantitative real-time polymerase chain reaction (q-RT-PCR) showed a significant increase in mRNA expression of osteocalcin (Ocn), Runx2, osteonectin (On) and osteopontin (Op) (p < 0.05) in the C3H10T1/2/Osx cells compared to the empty vector transfected cell control. At day 21, mineralization was demonstrated in the cultures of C3H10T1/2/Osx exposed to dex, but neither in cultures lacking dex nor controls. In the absence of dex, C3H10T1/2/Osx cells revealed a significantly higher expression of Sox9 and Aggrecan (Agc). In vivo, 80 microg of Osx plasmid DNA induced heterotopic mineralization 4 weeks following implantation in a mouse muscle model and the effect was dependent on the Osx plasmid DNA dose delivered in the PLGA scaffold. Using a non-committed cell line (C3H10T1/2), cell differentiation to an osteoblast phenotype appears to be dependent upon an interaction between intracellular events initiated by the transcriptional factor Osx and the presence of dex. The in vivo findings suggest Osx may promote osteoblast differentiationand mineralization at a heterotopic site.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1549-3296
pubmed:author
pubmed:copyrightInfo
Copyright 2007 Wiley Periodicals, Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
83
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
770-8
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Osteoblast differentiation in vitro and in vivo promoted by Osterix.
pubmed:affiliation
Bone Tissue Engineering Center, Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural