Transformation of resident notochord‐descendent nucleus pulposus cells in mouse injury‐induced fibrotic intervertebral discs

Abstract

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PRIMUS: Comprehensive proteomics of mouse intervertebral discs that inform novel biology and relevance to human disease modelling

“…Nonetheless, there are studies indicating that mouse NPs do become less cellular with ageing, as demonstrated in inbred SM/J mice [17] and genetically modified strains such as premature ‘disc degeneration’ in mice with notochord-specific deletion of Ccn2, conditionally deleted Sox9 in Acan -expressing cells, or caveolin-1 -null mice [66] , [67] , [68] . Further, in injury (IVD puncture) or mechanical-loading induced degeneration (tail looping) [67] mouse models for IDD, there is a loss of the vacuolated NLCs and a shift towards cells with chondrogenic and fibroblastic characteristics [26] , which is also observed in human discs in ageing and degeneration [7] , [8] . Thus, despite a comparable postnatal stage in terms of sexual maturity, the 8-week mouse and the 16yo human NPs are vastly different, and that the former may reflect a younger version of the latter.…”

“…To achieve a comprehensive characterization of a “healthy” mouse IVD, we performed label-free deep proteomics (by LC-MS/MS; Methods and Supplementary materials ) on NP and AF of 8-week-old Foxa2 mNE -Cre/ZEG mice (on mixed C57BL/6J and B6CBAF1/J backgrounds) [26] , in which the NP are tagged by enhanced green fluorescent protein (eGFP). This was followed by systemic analyses and validation ( Fig.…”

“…Care of animals was in accordance with institution guidelines at the Centre for Comparative Medicine Research, which is an AAALAC International accredited service centre. To guide a visual and specific isolation of the NP and dissection of the AF, we used an in-house generated Foxa2 mNE -Cre mouse model [26] crossed with the Z/EG reporter mouse to genetically tag notochord cells and descendants by the expression of the enhanced green fluorescent protein (eGFP). Eight-week-old Foxa2 mNE -Cre/ZEG male and female mice were sacrificed and healthy tail and lumbar IVDs isolated and processed as independent samples.…”

Mesenchymal Stem Cell-Derived Exosomes as a Novel Strategy for the Treatment of Intervertebral Disc Degeneration

“…The incidence and prevalence of LBP in China have increased annually, and it has become one of the major diseases that affect both public health and people’s quality of life ( Yao et al, 2011 ; Wu et al, 2019 ). Previous studies ( Liao et al, 2019a ; Au et al, 2020 ; Binch et al, 2021 ; Croft et al, 2021 ) showed that intervertebral disc (IVD) degeneration (IVDD) is the most prevalent contributor to LBP at present. Although the etiology of IVDD remains poorly understood, some influencing factors include metabolic disorders, aging, mechanical loading, trauma, infection, nutrition, and genetic predisposition ( Deyo and Weinstein, 2001 ; Cherif et al, 2020 ).…”

Fibrotic alterations in human annulus fibrosus correlate with progression of intervertebral disc herniation

“…MFs express alpha-smooth muscle actin (α-SMA) [ 21 ] and are responsible for extensive ECM deposition, namely collagen, within fibrotic tissue, altering tissue architecture and function [ 21 – 23 ]. In the IVD, upon injury, MFs have been suggested to be involved in the AF repair process [ 24 , 25 ]. The presence of α-SMA+ cells in IVD herniation has also been studied, being increased in degenerated and extruded IVDs, both in human and rat [ 12 ].…”