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1.

C-type natriuretic peptide regulates endochondral ossification through p38 MAP kinase-dependent pathways_2

(Submitter supplied) C-type natriuretic peptide (CNP) has been recently identified as an important anabolic regulator of endochondral bone growth, but the molecular mechanism mediating these effects are not completely understood. Here we demonstrate that CNP activates the p38 MAP kinase pathway in chondrocytes and that pharmacological inhibition of p38 blocks the anabolic effects of CNP in a tibia organ culture system. We further show that CNP stimulates endochondral bone growth largely through expansion of the hypertrophic zone of the growth plate, while delaying mineralization. Both effects are reversed by p38 inhibition. We performed Affymetrix microarray analyses to identify CNP target genes in the organ culture system. These studies confirmed that hypertrophic chondrocytes are the main targets of CNP signaling in the growth plate, potentially because cGMP-dependent kinases I and II, important transducers of CNP signaling and are expressed at much higher levels in these cells than in other areas of the tibia. One of the genes most strongly induced by CNP was the Ptgs2 gene, encoding Cox2. Real-time PCR confirmed that Cox2 expression was induced by CNP in hypertrophic chondrocytes, but surprisingly in a p38-independent manner. Moreover, Cox2 inhibition – in contrast to p38 inhibition - did not block the anabolic effects of CNP. In summary, our data identify novel target genes of CNP and demonstrate that the p38 pathway is a novel, essential mediator of CNP effects on endochondral ossification, with potential implications for numerous skeletal diseases. Keywords: Growth plate zone comparison and treatment response analysis
Organism:
Mus musculus
Type:
Expression profiling by array
Platform:
GPL1261
18 Samples
Download data: CEL, EXP
Series
Accession:
GSE4481
ID:
200004481
2.

[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array

(Submitter supplied) Affymetrix submissions are typically submitted to GEO using the GEOarchive method described at http://0-www.ncbi.nlm.nih.gov.brum.beds.ac.uk/projects/geo/info/geo_affy.html June 03, 2009: annotation table updated with netaffx build 28 June 07, 2012: annotation table updated with netaffx build 32 June 23, 2016: annotation table updated with netaffx build 35 Protocol: see manufacturer's web site All probe sets represented on the GeneChip Mouse Expression Set 430 are included on the GeneChip Mouse Genome 430 2.0 Array. more...
Organism:
Mus musculus
601 DataSets
4431 Series
40 Related Platforms
57738 Samples
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Platform
Accession:
GPL1261
ID:
100001261
3.

3BSA H

Organism:
Mus musculus
Source name:
662
Platform:
GPL1261
Series:
GSE4481
Download data: CEL, EXP
Sample
Accession:
GSM100197
ID:
300100197
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