Silencing Dkk1 expression rescues dexamethasone-induced suppression of primary human osteoblast differentiation.

Hdl Handle:
http://hdl.handle.net/10147/135673
Title:
Silencing Dkk1 expression rescues dexamethasone-induced suppression of primary human osteoblast differentiation.
Authors:
Butler, Joseph S; Queally, Joseph M; Devitt, Brian M; Murray, David W; Doran, Peter P; O'Byrne, John M
Affiliation:
Clinical Research Centre, UCD School of Medicine & Medical Science, Mater Misericordiae University Hospital, Dublin, Ireland. josephsbutler@hotmail.com
Citation:
Silencing Dkk1 expression rescues dexamethasone-induced suppression of primary human osteoblast differentiation. 2010, 11:210 BMC Musculoskelet Disord
Journal:
BMC musculoskeletal disorders
Issue Date:
Sep-2010
URI:
http://hdl.handle.net/10147/135673
DOI:
10.1186/1471-2474-11-210
PubMed ID:
20843343
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/20843343
Abstract:
The Wnt/β-catenin pathway is a major signaling cascade in bone biology, playing a key role in bone development and remodeling. The objectives of this study were firstly, to determine the effects of dexamethasone exposure on Wnt/β-catenin signaling at an intracellular and transcriptional level, and secondly, to assess the phenotypic effects of silencing the Wnt antagonist, Dickkopf-1 (Dkk1) in the setting of dexamethasone exposure.; Primary human osteoblasts were exposed in vitro to 10-8 M dexamethasone over a 72 h time course. The phenotypic marker of osteoblast differentiation was analyzed was alkaline phosphatase activity. Intracellular β-catenin trafficking was assessed using immunoflourescence staining and TCF/LEF mediated transcription was analyzed using a Wnt luciferase reporter assay. Dkk1 expression was silenced using small interfering RNA (siRNA).; Primary human osteoblasts exposed to dexamethasone displayed a significant reductions in alkaline phosphatase activity over a 72 h time course. Immunoflourescence analaysis of β-catenin localization demonstrated a significant reduction in intracytosolic and intranuclear β-catenin in response to dexamethasone exposure. These changes were associated with a reduction of TCF/LEF mediated transcription. Silencing Dkk1 expression in primary human osteoblasts exposed to dexamethasone resulted in an increase in alkaline phosphatase activity when compared to scrambled control.; Wnt/β-catenin signaling plays a key role in regulating glucocorticoid-induced osteoporosis in vitro. Silencing Dkk1 expression rescues dexamethasone-induced suppression of primary human osteoblast differentiation. Targeting of the Wnt/β-catenin signaling pathway offers an exciting opportunity to develop novel anabolic bone agents to treat osteoporosis and disorders of bone mass.
Item Type:
Article
Language:
en
MeSH:
Cell Differentiation; Cells, Cultured; Dexamethasone; Gene Expression Regulation; Gene Silencing; Growth Inhibitors; Humans; Intercellular Signaling Peptides and Proteins; Osteoblasts
ISSN:
1471-2474

Full metadata record

DC FieldValue Language
dc.contributor.authorButler, Joseph Sen
dc.contributor.authorQueally, Joseph Men
dc.contributor.authorDevitt, Brian Men
dc.contributor.authorMurray, David Wen
dc.contributor.authorDoran, Peter Pen
dc.contributor.authorO'Byrne, John Men
dc.date.accessioned2011-07-08T13:36:22Z-
dc.date.available2011-07-08T13:36:22Z-
dc.date.issued2010-09-
dc.identifier.citationSilencing Dkk1 expression rescues dexamethasone-induced suppression of primary human osteoblast differentiation. 2010, 11:210 BMC Musculoskelet Disorden
dc.identifier.issn1471-2474-
dc.identifier.pmid20843343-
dc.identifier.doi10.1186/1471-2474-11-210-
dc.identifier.urihttp://hdl.handle.net/10147/135673-
dc.description.abstractThe Wnt/β-catenin pathway is a major signaling cascade in bone biology, playing a key role in bone development and remodeling. The objectives of this study were firstly, to determine the effects of dexamethasone exposure on Wnt/β-catenin signaling at an intracellular and transcriptional level, and secondly, to assess the phenotypic effects of silencing the Wnt antagonist, Dickkopf-1 (Dkk1) in the setting of dexamethasone exposure.-
dc.description.abstractPrimary human osteoblasts were exposed in vitro to 10-8 M dexamethasone over a 72 h time course. The phenotypic marker of osteoblast differentiation was analyzed was alkaline phosphatase activity. Intracellular β-catenin trafficking was assessed using immunoflourescence staining and TCF/LEF mediated transcription was analyzed using a Wnt luciferase reporter assay. Dkk1 expression was silenced using small interfering RNA (siRNA).-
dc.description.abstractPrimary human osteoblasts exposed to dexamethasone displayed a significant reductions in alkaline phosphatase activity over a 72 h time course. Immunoflourescence analaysis of β-catenin localization demonstrated a significant reduction in intracytosolic and intranuclear β-catenin in response to dexamethasone exposure. These changes were associated with a reduction of TCF/LEF mediated transcription. Silencing Dkk1 expression in primary human osteoblasts exposed to dexamethasone resulted in an increase in alkaline phosphatase activity when compared to scrambled control.-
dc.description.abstractWnt/β-catenin signaling plays a key role in regulating glucocorticoid-induced osteoporosis in vitro. Silencing Dkk1 expression rescues dexamethasone-induced suppression of primary human osteoblast differentiation. Targeting of the Wnt/β-catenin signaling pathway offers an exciting opportunity to develop novel anabolic bone agents to treat osteoporosis and disorders of bone mass.-
dc.language.isoenen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/20843343en
dc.subject.meshCell Differentiation-
dc.subject.meshCells, Cultured-
dc.subject.meshDexamethasone-
dc.subject.meshGene Expression Regulation-
dc.subject.meshGene Silencing-
dc.subject.meshGrowth Inhibitors-
dc.subject.meshHumans-
dc.subject.meshIntercellular Signaling Peptides and Proteins-
dc.subject.meshOsteoblasts-
dc.titleSilencing Dkk1 expression rescues dexamethasone-induced suppression of primary human osteoblast differentiation.en
dc.typeArticleen
dc.contributor.departmentClinical Research Centre, UCD School of Medicine & Medical Science, Mater Misericordiae University Hospital, Dublin, Ireland. josephsbutler@hotmail.comen
dc.identifier.journalBMC musculoskeletal disordersen
dc.description.provinceLeinster-

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