The synovial microenvironment of osteoarthritic joints alters RNA-seq expression profiles of human primary articular chondrocytes

Eric A. Lewallen, Carolina A. Bonin, Xin Li, Jay Smith, Marcel Karperien, A. Noelle Larson, David G. Lewallen, Simon M. Cool, Jennifer J. Westendorf, Aaron J. Krych, Alexey A. Leontovich, Hee Jeong Im, Andre J. van Wijnen

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Osteoarthritis (OA) is a disabling degenerative joint disease that prompts pain and has limited treatment options. To permit early diagnosis and treatment of OA, a high resolution mechanistic understanding of human chondrocytes in normal and diseased states is necessary. In this study, we assessed the biological effects of OA-related changes in the synovial microenvironment on chondrocytes embedded within anatomically intact cartilage from joints with different pathological grades by next generation RNA-sequencing (RNA-seq). We determined the transcriptome of primary articular chondrocytes derived from anatomically unaffected knees and ankles, as well as from joints affected by OA. The GALAXY bioinformatics platform was used to facilitate biological interpretations. Comparisons of patient samples by k-means, hierarchical clustering and principal component analyses together reveal that primary chondrocytes exhibit OA grade-related differences in gene expression, including genes involved in cell-adhesion, ECM production and immune response. We conclude that diseased synovial microenvironments in joints with different histopathological OA grades directly alter gene expression in chondrocytes. One ramification of this finding is that anatomically intact cartilage from OA joints is not an ideal source of healthy chondrocytes, nor should these specimens be used to generate a normal baseline for the molecular characterization of diseased joints.

Original languageEnglish (US)
Pages (from-to)456-464
Number of pages9
JournalGene
Volume591
Issue number2
DOIs
StatePublished - Oct 15 2016

Keywords

  • Cartilage
  • Cell adhesion
  • Collins grade
  • ECM
  • Galaxy

ASJC Scopus subject areas

  • Genetics

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