A Membranome-Centered Approach Defines Novel Biomarkers for Cellular Subtypes in the Intervertebral Disc

Guus G. H. van den Akker, Lars M. T. Eijssen, Stephen M. Richardson, Lodewijk W. van Rhijn, Judith A. Hoyland, Tim J. M. Welting, Jan Willem Voncken*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Web of Science)

Abstract

Objective

Lack of specific marker-sets prohibits definition and functional distinction of cellular subtypes in the intervertebral disc (IVD), such as those from the annulus fibrosus (AF) and the nucleus pulposus (NP).

Design

We recently generated immortalized cell lines from human NP and AF tissues; these comprise a set of functionally distinct clonal subtypes. Whole transcriptome analyses were performed of 12 phenotypically distinct clonal cell lines (4x NP-Responder, 4x NP-nonResponder, 2x AF-Sheet forming, and 2x AF-nonSheet forming). Data sets were filtered for membrane-associated marker genes and compared to literature.

Results

Comparison of our immortal cell lines to published primary NP, AF, and articular chondrocytes (AC) transcriptome datasets revealed preservation of AF and NP phenotypes. NP-specific membrane-associated genes were defined by comparison to AF cells in both the primary dataset (46 genes) and immortal cell-lines (161 genes). Definition of AF-specific membrane-associated genes yielded 125 primary AF cell and 92 immortal cell-line markers. Overlap between primary and immortal NP cells yielded high-confidence NP-specific marker genes for NP-R (CLDN11, TMEFF2, CA12, ANXA2, CD44) and NP-nR (EFNA1, NETO2, SLC2A1). Overlap between AF and immortal AF subtypes yielded specific markers for AF-S (COLEC12, LPAR1) and AF-nS (CHIC1).

Conclusions

The current study provides a reference platform for preclinical evaluation of novel membrane-associated cell type-specific markers in the IVD. Future research will focus on their biological relevance for IVD function in development, homeostasis, and degenerate conditions.

Original languageEnglish
Pages (from-to)203-220
Number of pages18
JournalCartilage
Volume11
Issue number2
DOIs
Publication statusPublished - Apr 2020

Keywords

  • intervertebral disc
  • cell lines
  • nucleus pulposus
  • annulus fibrosus
  • biomarkers
  • membranome
  • NUCLEUS PULPOSUS CELLS
  • LOW-BACK-PAIN
  • EXTRACELLULAR-MATRIX
  • GENE-EXPRESSION
  • STEM-CELLS
  • IN-VITRO
  • PROGENITOR CELLS
  • ANNULUS FIBROSUS
  • CARTILAGE CELLS
  • FUNCTIONAL-ROLE

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