Molecular pathology of human knee arthrofibrosis defined by RNA sequencing

Banu Bayram, Afton K. Limberg, Christopher G. Salib, Jacob W. Bettencourt, William H. Trousdale, Eric A. Lewallen, Nicolas Reina, Christopher R. Paradise, Roman Thaler, Mark E. Morrey, Joaquin Sanchez-Sotelo, Daniel J. Berry, Andre J. van Wijnen, Matthew P. Abdel

Research output: Contribution to journalReview article

1 Scopus citations

Abstract

Arthrofibrosis is an abnormal histopathologic response, is debilitating for patients, and poses a substantial unsolved clinical challenge. This study characterizes molecular biomarkers and regulatory pathways associated with arthrofibrosis by comparing fibrotic and non-fibrotic human knee tissue. The fibrotic group encompasses 4 patients undergoing a revision total knee arthroplasty (TKA) for arthrofibrosis (RTKA-A) while the non-fibrotic group includes 4 patients undergoing primary TKA for osteoarthritis (PTKA) and 4 patients undergoing revision TKA for non-arthrofibrotic and non-infectious etiologies (RTKA-NA). RNA-sequencing of posterior capsule specimens revealed differences in gene expression between each patient group by hierarchical clustering, principal component analysis, and correlation analyses. Multiple differentially expressed genes (DEGs) were defined in RTKA-A versus PTKA patients (i.e., 2059 up-regulated and 1795 down-regulated genes) and RTKA-A versus RTKA-NA patients (i.e., 3255 up-regulated and 3683 down-regulated genes). Our findings define molecular and pathological markers of arthrofibrosis, as well as novel potential targets for risk profiling, early diagnosis and pharmacological treatment of patients.

Original languageEnglish (US)
Pages (from-to)2703-2712
Number of pages10
JournalGenomics
Volume112
Issue number4
DOIs
StatePublished - Jul 2020

Keywords

  • Acquired idiopathic stiffness
  • DEGs
  • Joint stiffness
  • RNA-seq
  • Total knee Arthroplasty

ASJC Scopus subject areas

  • Genetics

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  • Cite this

    Bayram, B., Limberg, A. K., Salib, C. G., Bettencourt, J. W., Trousdale, W. H., Lewallen, E. A., Reina, N., Paradise, C. R., Thaler, R., Morrey, M. E., Sanchez-Sotelo, J., Berry, D. J., van Wijnen, A. J., & Abdel, M. P. (2020). Molecular pathology of human knee arthrofibrosis defined by RNA sequencing. Genomics, 112(4), 2703-2712. https://doi.org/10.1016/j.ygeno.2020.03.004