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Matrix Biol. 2018 Sep;70:123-139. doi: 10.1016/j.matbio.2018.03.024. Epub 2018 Apr 9.

Early onset of disc degeneration in SM/J mice is associated with changes in ion transport systems and fibrotic events.

Author information

1
School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
2
Centre for Genomic Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
3
Department of Orthopaedic Surgery, Washington University, St. Louis, MO 63110, USA.
4
Department of Biology, Loyola University of Chicago, IL 60660, USA.
5
Department of Genetics, Washington University, St. Louis, MO 63110, USA.
6
School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China; The University of Hong Kong - Shenzhen Institute of Research and Innovation (HKU-SIRI), Hi-Tech Industrial Park, Nanshan, Shenzhen, China.
7
School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China; The University of Hong Kong - Shenzhen Institute of Research and Innovation (HKU-SIRI), Hi-Tech Industrial Park, Nanshan, Shenzhen, China. Electronic address: chand@hku.hk.

Abstract

Intervertebral disc degeneration (IDD) causes back pain and sciatica, affecting quality of life and resulting in high economic/social burden. The etiology of IDD is not well understood. Along with aging and environmental factors, genetic factors also influence the onset, progression and severity of IDD. Genetic studies of risk factors for IDD using human cohorts are limited by small sample size and low statistical power. Animal models amenable to genetic and functional studies of IDD provide desirable alternatives. Despite differences in size and cellular content as compared to human intervertebral discs (IVDs), the mouse is a powerful model for genetics and assessment of cellular changes relevant to human biology. Here, we provide evidence for early onset disc degeneration in SM/J relative to LG/J mice with poor and good tissue healing capacity respectively. In the first few months of life, LG/J mice maintain a relatively constant pool of notochordal-like cells in the nucleus pulposus (NP) of the IVD. In contrast, chondrogenic events are observed in SM/J mice beginning as early as one-week-old, with progressive fibrotic changes. Further, the extracellular matrix changes in the NP are consistent with IVD degeneration. Leveraging on the genomic data of two parental and two recombinant inbred lines, we assessed the genetic contribution to the NP changes and identified processes linked to the regulation of ion transport systems. Significantly, "transport" system is also in the top three gene ontology (GO) terms from a comparative proteomic analysis of the mouse NP. These findings support the potential of the SM/J, LG/J and their recombinant inbred lines for future genetic and biological analysis in mice and validation of candidate genes and biological relevance in human cohort studies. The proteomic data has been deposited to the ProteomeXchange Consortium via the PRIDE [1] partner repository with the dataset identifier PXD008784.

KEYWORDS:

Fibrosis; Genetics; Intervertebral disc; Ion transport; Matrisome; SM/J

PMID:
29649547
DOI:
10.1016/j.matbio.2018.03.024
[Indexed for MEDLINE]

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