Systems Genetics Analysis of Mouse Chondrocyte Differentiation
One of the goals of systems genetics is the reconstruction of gene networks that underlie key processes in development and disease. To identify cartilage gene networks that play an important role in bone development, we used a systems genetics approach that integrated microarray gene expression prof...
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2011
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pubmed-31793272012-04-01 Systems Genetics Analysis of Mouse Chondrocyte Differentiation Suwanwela, Jaijam Farber, Charles R Haung, Bau-lin Song, Buer Pan, Calvin Lyons, Karen M Lusis, Aldons J Original Article One of the goals of systems genetics is the reconstruction of gene networks that underlie key processes in development and disease. To identify cartilage gene networks that play an important role in bone development, we used a systems genetics approach that integrated microarray gene expression profiles from cartilage and bone phenotypic data from two sets of recombinant inbred strains. Microarray profiles generated from isolated chondrocytes were used to generate weighted gene coexpression networks. This analysis resulted in the identification of subnetworks (modules) of coexpressed genes that then were examined for relationships with bone geometry and density. One module exhibited significant correlation with femur length (r = 0.416), anteroposterior diameter (r = 0.418), mediolateral diameter (r = 0.576), and bone mineral density (r = 0.475). Highly connected genes (n = 28) from this and other modules were tested in vitro using prechondrocyte ATDC5 cells and RNA interference. Five of the 28 genes were found to play a role in chondrocyte differentiation. Two of these, Hspd1 and Cdkn1a, were known previously to function in chondrocyte development, whereas the other three, Bhlhb9, Cugbp1, and Spcs3, are novel genes. Our integrative analysis provided a systems-level view of cartilage development and identified genes that may be involved in bone development. © 2011 American Society for Bone and Mineral Research. Wiley Subscription Services, Inc., A Wiley Company 2011-04 2010-10-14 /pmc/articles/PMC3179327/ /pubmed/20954177 http://dx.doi.org/10.1002/jbmr.271 Text en Copyright © 2011 American Society for Bone and Mineral Research http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. |
repository_type |
Open Access Journal |
institution_category |
Foreign Institution |
institution |
US National Center for Biotechnology Information |
building |
NCBI PubMed |
collection |
Online Access |
language |
English |
format |
Online |
author |
Suwanwela, Jaijam Farber, Charles R Haung, Bau-lin Song, Buer Pan, Calvin Lyons, Karen M Lusis, Aldons J |
spellingShingle |
Suwanwela, Jaijam Farber, Charles R Haung, Bau-lin Song, Buer Pan, Calvin Lyons, Karen M Lusis, Aldons J Systems Genetics Analysis of Mouse Chondrocyte Differentiation |
author_facet |
Suwanwela, Jaijam Farber, Charles R Haung, Bau-lin Song, Buer Pan, Calvin Lyons, Karen M Lusis, Aldons J |
author_sort |
Suwanwela, Jaijam |
title |
Systems Genetics Analysis of Mouse Chondrocyte Differentiation |
title_short |
Systems Genetics Analysis of Mouse Chondrocyte Differentiation |
title_full |
Systems Genetics Analysis of Mouse Chondrocyte Differentiation |
title_fullStr |
Systems Genetics Analysis of Mouse Chondrocyte Differentiation |
title_full_unstemmed |
Systems Genetics Analysis of Mouse Chondrocyte Differentiation |
title_sort |
systems genetics analysis of mouse chondrocyte differentiation |
description |
One of the goals of systems genetics is the reconstruction of gene networks that underlie key processes in development and disease. To identify cartilage gene networks that play an important role in bone development, we used a systems genetics approach that integrated microarray gene expression profiles from cartilage and bone phenotypic data from two sets of recombinant inbred strains. Microarray profiles generated from isolated chondrocytes were used to generate weighted gene coexpression networks. This analysis resulted in the identification of subnetworks (modules) of coexpressed genes that then were examined for relationships with bone geometry and density. One module exhibited significant correlation with femur length (r = 0.416), anteroposterior diameter (r = 0.418), mediolateral diameter (r = 0.576), and bone mineral density (r = 0.475). Highly connected genes (n = 28) from this and other modules were tested in vitro using prechondrocyte ATDC5 cells and RNA interference. Five of the 28 genes were found to play a role in chondrocyte differentiation. Two of these, Hspd1 and Cdkn1a, were known previously to function in chondrocyte development, whereas the other three, Bhlhb9, Cugbp1, and Spcs3, are novel genes. Our integrative analysis provided a systems-level view of cartilage development and identified genes that may be involved in bone development. © 2011 American Society for Bone and Mineral Research. |
publisher |
Wiley Subscription Services, Inc., A Wiley Company |
publishDate |
2011 |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179327/ |
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1611477134254014464 |