Transcriptional profiling differences for articular cartilage and repair tissue in equine joint surface lesions

Michael J. Mienaltowski, Liping Huang, David D. Frisbie, C. Wayne McIlwraith, Arnold J. Stromberg, Arne C. Bathke, James N. MacLeod

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Background. Full-thickness articular cartilage lesions that reach to the subchondral bone yet are restricted to the chondral compartment usually fill with a fibrocartilage-like repair tissue which is structurally and biomechanically compromised relative to normal articular cartilage. The objective of this study was to evaluate transcriptional differences between chondrocytes of normal articular cartilage and repair tissue cells four months post-microfracture. Methods. Bilateral one-cm2 full-thickness defects were made in the articular surface of both distal femurs of four adult horses followed by subchondral microfracture. Four months postoperatively, repair tissue from the lesion site and grossly normal articular cartilage from within the same femorotibial joint were collected. Total RNA was isolated from the tissue samples, linearly amplified, and applied to a 9,413-probe set equine-specific cDNA microarray. Eight paired comparisons matched by limb and horse were made with a dye-swap experimental design with validation by histological analyses and quantitative real-time polymerase chain reaction (RT-qPCR). Results. Statistical analyses revealed 3,327 (35.3%) differentially expressed probe sets. Expression of biomarkers typically associated with normal articular cartilage and fibrocartilage repair tissue corroborate earlier studies. Other changes in gene expression previously unassociated with cartilage repair were also revealed and validated by RT-qPCR. Conclusion. The magnitude of divergence in transcriptional profiles between normal chondrocytes and the cells that populate repair tissue reveal substantial functional differences between these two cell populations. At the four-month postoperative time point, the relative deficiency within repair tissue of gene transcripts which typically define articular cartilage indicate that while cells occupying the lesion might be of mesenchymal origin, they have not recapitulated differentiation to the chondrogenic phenotype of normal articular chondrocytes.

Original languageEnglish
Article number60
JournalBMC Medical Genomics
Volume2
DOIs
StatePublished - 2009

Bibliographical note

Funding Information:
Dr. Mark Band and the W.M. Keck Center for Comparative and Functional Genomics at the University of Illinois are graciously acknowledged. The authors also appreciate Rebekah Cosden for her insight into RNA isolation of small samples and Dr. Timothy McClintock for his advice in functional genomics analysis. Financial support was received from the Gluck Equine Research Foundation, The Geoffrey C. Hughes Foundation, The Morris Animal Foundation (Training Fellowship D06EQ-409 to M.M. and the Consortium for Equine Medical Genetics D07EQ-500), and the NIH (KY-INBRE P20 RR16481).

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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