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Series GSE9247 Query DataSets for GSE9247
Status Public on Oct 06, 2007
Title Effect of histone deacetylase inhibitors on osteoblast gene expression
Organism Mus musculus
Experiment type Expression profiling by array
Summary Background:
Osteoblast differentiation requires the coordinated stepwise expression of multiple genes. Histone deacetylase inhibitors (HDIs) accelerate the osteoblast differentiation process by blocking the activity of histone deacetylases (HDACs), which alter gene expression by modifying chromatin structure. We previously demonstrated that HDIs and HDAC3 shRNAs accelerate matrix mineralization and the expression of osteoblast maturation genes (e.g. alkaline phosphatase, osteocalcin). Identifying other genes that are differentially regulated by HDIs might identify new pathways that contribute to osteoblast differentiation.

Results:
To identify other osteoblast genes that are altered early by HDIs, we incubated MC3T3-E1 preosteoblasts with HDIs (trichostatin A, MS-275, or valproic acid) for 18 hours in osteogenic conditions. The promotion of osteoblast differentiation by HDIs in this experiment was confirmed by osteogenic assays. Gene expression profiles relative to vehicle-treated cells were assessed by microarray analysis with Affymetrix GeneChip 430 2.0 arrays. The regulation of several genes by HDIs in MC3T3-E1 cells and primary osteoblasts was verified by quantitative real-time PCR. Nine genes were differentially regulated by at least two-fold after exposure to each of the three HDIs and six were verified by PCR in osteoblasts. Four of the verified genes (solute carrier family 9 isoform 3 regulator 1 (Slc9a3r1), sorbitol dehydrogenase 1, a kinase anchor protein, and glutathione S-transferase alpha 4) were induced. Two genes (proteasome subunit, beta type 10 and adaptor-related protein complex AP-4 sigma 1) were suppressed. We also identified eight growth factors and growth factor receptor genes that are significantly altered by each of the HDIs, including Frizzled related proteins 1 and 4, which modulate the Wnt signaling pathway.

Conclusions: This study identifies osteoblast genes that are regulated early by HDIs and indicates pathways that might promote osteoblast maturation following HDI exposure. One gene whose upregulation following HDI treatment is consistent with this notion is Slc9a3r1. Also known as NHERF1, Slc9a3r1 is required for optimal bone density. Similarly, the regulation of Wnt receptor genes indicates that this crucial pathway in osteoblast development is also affected by HDIs. These data support the hypothesis that HDIs regulate the expression of genes that promote osteoblast differentiation and maturation.
Keywords: gene expression
 
Overall design To identify other osteoblast genes that are altered early by HDIs, we incubated MC3T3-E1 preosteoblasts with HDIs (trichostatin A, MS-275, or valproic acid) or the vehicle control (DMSO) for 18 hours in osteogenic conditions. Gene expression profiles relative to vehicle-treated cells were assessed in triplicate (in some cases quadruplicate) samples by microarray analysis with Affymetrix GeneChip 430 2.0 arrays.
 
Contributor(s) Westendorf JJ, Schroeder TM, Nair AK, Staggs R, Lamblin A
Citation(s) 17925016
Submission date Oct 05, 2007
Last update date Feb 11, 2019
Contact name Jennifer J Westendorf
Organization name Mayo Clinic
Street address 200 First Street SW
City Rochester
State/province MN
ZIP/Postal code 55905
Country USA
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (15)
GSM234794 DMSO Treated Control 1
GSM234795 DMSO Treated Control 2
GSM234796 DMSO Treated Control 3
Relations
BioProject PRJNA102859

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE9247_RAW.tar 86.3 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
Raw data provided as supplementary file

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