title: EGR1 controls divergent cellular responses of distinctive nucleus pulposus cell types.
abstract: BACKGROUND
  Immediate early genes (IEGs) encode transcription factors which serve as first line response modules to altered conditions and mediate appropriate cell responses. The immediate early response gene EGR1 is involved in physiological adaptation of numerous different cell types. We have previously shown a role for EGR1 in controlling processes supporting chondrogenic differentiation. We recently established a unique set of phenotypically distinct cell lines from the human nucleus pulposus (NP). Extensive characterization showed that these NP cellular subtypes represented progenitor-like cell types and more functionally mature cells.
  
  
  METHODS
  To further understanding of cellular heterogeneity in the NP, we analyzed the response of these cell subtypes to anabolic and catabolic factors. Here, we test the hypothesis that physiological responses of distinct NP cell types are mediated by EGR1 and reflect specification of cell function using an RNA interference-based experimental approach.
  
  
  RESULTS
  We show that distinct NP cell types rapidly induce EGR1 exposure to either growth factors or inflammatory cytokines. In addition, we show that mRNA profiles induced in response to anabolic or catabolic conditions are cell type specific: the more mature NP cell type produced a strong and more specialized transcriptional response to IL-1β than the NP progenitor cells and aspects of this response were controlled by EGR1.
  
  
  CONCLUSIONS
  Our current findings provide important substantiation of differential functionality among NP cellular subtypes. Additionally, the data shows that early transcriptional programming initiated by EGR1 is essentially restrained by the cells' epigenome as it was determined during development and differentiation. These studies begin to define functional distinctions among cells of the NP and will ultimately contribute to defining functional phenotypes within the adult intervertebral disc.
authors.affiliation: Department of Orthopaedic Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.|Department of Molecular Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.|Current Address: Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Guus G H
authors.initials: GG
authors.lastname: van den Akker
authors.affiliation: Department of Orthopaedic Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Don A M
authors.initials: DA
authors.lastname: Surtel
authors.affiliation: Department of Orthopaedic Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Andy
authors.initials: A
authors.lastname: Cremers
authors.affiliation: Department of Molecular Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Martijn F G A
authors.initials: MF
authors.lastname: Hoes
authors.affiliation: Department of Orthopaedic Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Marjolein M
authors.initials: MM
authors.lastname: Caron
authors.affiliation: Centre for Tissue Injury and Repair, Institute of Inflammation and Repair, The University of Manchester, Manchester, UK.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Richardson
authors.affiliation: Centre for Tissue Injury and Repair, Institute of Inflammation and Repair, The University of Manchester, Manchester, UK.|Current Address: Department of Orthopaedics, Centro Hospitalar do Porto - Hospital de Santo António, Porto, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Rodrigues-Pinto
authors.affiliation: Department of Orthopaedic Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Lodewijk W
authors.initials: LW
authors.lastname: van Rhijn
authors.affiliation: Centre for Tissue Injury and Repair, Institute of Inflammation and Repair, The University of Manchester, Manchester, UK.|NIHR Manchester Musculoskeletal Biomedical Research Unit, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Hoyland
authors.affiliation: Department of Orthopaedic Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Tim J M
authors.initials: TJ
authors.lastname: Welting
authors.affiliation: Department of Molecular Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands. w.voncken@maastrichtuniversity.nl.
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Voncken
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D007403:Intervertebral Disc / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D034622:RNA Interference; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta
keywords: Cell line; Differentiation; EGR1; IL-1β; Inflammation; Intervertebral disc; Nucleus pulposus; Specific cell responses