Molecular characterization of physis tissue by RNA sequencing

Christopher R. Paradise, Catalina Galeano-Garces, Daniela Galeano-Garces, Amel Dudakovic, Todd A. Milbrandt, Daniel B.F. Saris, Aaron J. Krych, Marcel Karperien, Gabriel B. Ferguson, Denis Evseenko, Scott M. Riester, Andre J. van Wijnen* (Corresponding Author), A. Noelle Larson (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

Abstract

The physis is a well-established and anatomically distinct cartilaginous structure that is crucial for normal long-bone development and growth. Abnormalities in physis function are linked to growth plate disorders and other pediatric musculoskeletal diseases. Understanding the molecular pathways operative in the physis may permit development of regenerative therapies to complement surgically-based procedures that are the current standard of care for growth plate disorders. Here, we performed next generation RNA sequencing on mRNA isolated from human physis and other skeletal tissues (e.g., articular cartilage and bone; n = 7 for each tissue). We observed statistically significant enrichment of gene sets in the physis when compared to the other musculoskeletal tissues. Further analysis of these upregulated genes identified physis-specific networks of extracellular matrix proteins including collagens (COL2A1, COL6A1, COL9A1, COL14A1, COL16A1) and matrilins (MATN1, MATN2, MATN3), and signaling proteins in the WNT pathway (WNT10B, FZD1, FZD10, DKK2) or the FGF pathway (FGF10, FGFR4). Our results provide further insight into the gene expression networks that contribute to the physis’ unique structural composition and regulatory signaling networks. Physis-specific expression profiles may guide ongoing initiatives in tissue engineering and cell-based therapies for treatment of growth plate disorders and growth modulation therapies. Furthermore, our findings provide new leads for therapeutic drug discovery that would permit future intervention through pharmacological rather than surgical strategies.

Original languageEnglish
Pages (from-to)87-96
Number of pages10
JournalGene
Volume668
DOIs
Publication statusPublished - 20 Aug 2018

Keywords

  • Bone
  • Cartilage
  • Growth plate
  • Physis
  • RNA sequencing

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    Paradise, C. R., Galeano-Garces, C., Galeano-Garces, D., Dudakovic, A., Milbrandt, T. A., Saris, D. B. F., ... Noelle Larson, A. (2018). Molecular characterization of physis tissue by RNA sequencing. Gene, 668, 87-96. https://doi.org/10.1016/j.gene.2018.05.034