Genome-wide study identifies the regulatory gene networks and signaling pathways from chondrocyte and peripheral blood monocyte of Kashin-Beck disease

Genes Cells. 2012 Aug;17(8):619-32. doi: 10.1111/j.1365-2443.2012.01620.x. Epub 2012 Jul 9.

Abstract

This investigation was designed to unravel gene networks in Kashin-Beck disease (KBD) and better identify target genes of KBD for gene therapy development. RNA was isolated separately from cartilage and peripheral blood samples of patients with KBD and healthy controls. Agilent 44K human whole-genome oligonucleotide microarrays were used to detect differentially expressed genes. Three significant canonical pathways and nine chondrocyte networks from chondrocytic gene expression profiles were screened using ingenuity pathway analysis (IPA), but only one network and no canonical pathways from peripheral blood monocytic gene profile were identified. Bak1, APAF-1, CASP6, IGFBP2, Col5a2 and TGFBI extracted from significant genes that involved in chondrocytic canonical pathways and networks may have closer relationship with the etiopathogenesis of KBD. Those genes may be potential targets for gene diagnosis and treatment. Six physiological functions were predominant and unique to the chondrocytic genes, whereas two were unique to peripheral blood monocytic genes. The identified genes may represent a source of potentially novel molecular targets, which may provide a better understanding of the molecular details in KBD pathogenesis and also provide useful pathways and network maps for the future research in osteochondrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / pathology
  • Case-Control Studies
  • Chondrocytes / pathology*
  • Female
  • Gene Expression Regulation
  • Gene Regulatory Networks*
  • Genome, Human
  • Genome-Wide Association Study
  • Humans
  • Kashin-Beck Disease / genetics*
  • Kashin-Beck Disease / metabolism
  • Kashin-Beck Disease / pathology
  • Male
  • Middle Aged
  • Monocytes / pathology*
  • Oligonucleotide Array Sequence Analysis
  • Signal Transduction*
  • Transcriptome