EGR1 controls divergent cellular responses of distinctive nucleus pulposus cell types

BMC Musculoskeletal Disorders

Research Article

Stephen M. Richardson¹  Ricardo Rodrigues-Pinto²  Judith A. Hoyland³  Martijn F. G. A. Hoes⁴  Jan Willem Voncken⁴  Andy Cremers⁵  Tim J. M. Welting⁵  Lodewijk W. van Rhijn⁵  Marjolein M. Caron⁵  Don A. M. Surtel⁵  Guus G. H. van den Akker⁶ 

[1] Centre for Tissue Injury and Repair, Institute of Inflammation and Repair, The University of Manchester, Manchester, UK;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;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;Department of Molecular Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands;Department of Orthopaedic Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands;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;

关键词: Intervertebral disc;    Nucleus pulposus;    Cell line;    EGR1;    Specific cell responses;    IL-1β;    Inflammation;    Differentiation;   

DOI  :  10.1186/s12891-016-0979-x

 received in 2015-08-14, accepted in 2016-03-09,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundImmediate 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.MethodsTo 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.ResultsWe 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.ConclusionsOur 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.

【 授权许可】

CC BY   
© van den Akker et al. 2016