Dataset Information

Matrisome remodelling during Intervertebral Disc development and ageing

ABSTRACT: Intervertebral disc (IVD) is often the cause of low back pain. Degeneration occurs with age and is accompanied by extracellular matrix (ECM) depletion, culminating in nucleus pulpous (NP) extrusion and IVD destruction. Although the changes that occur with ageing in the IVD have been under study, not much attention has been given to ECM remodelling during normal development. Therefore, a thorough study of ECM composition and a comprehensive view on how this microenvironment is affected in normal ageing conditions is needed, to better understand the processes involved in IVD development and in age-associated degeneration. We have compared the NP matrisome of bovine IVDs from foetus, young and old animals by quantitative iTRAQ LC-MS/MS. Protein expression levels of the most interesting candidates were validated by Western Blot analysis. In total, 161 bovine proteins were identified. Of these, 77 molecules were common to the three different age groups, of which 36 defined the NP matrisome. Differential expression levels obtained for Collagen Type XI, XII, XIV, Fibronectin and Prolargin were independently confirmed. Herein, we demonstrate a shift in NP matrisome signatures that occurs in healthy bovine IVDs with development and ageing. Thus, this study provides insight into factors that may explain age-associated IVD degeneration, and which are putative targets for therapy. It also highlights key molecules, characteristic of early developmental stages, which constitute potential effectors in IVD regeneration.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Bos Taurus (bovine)

TISSUE(S): Nucleus Pulposus

SUBMITTER: Cátia Santa

LAB HEAD: Bruno Manadas

PROVIDER: PXD004922 | Pride | 2017-09-25

REPOSITORIES: Pride

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Matrisome Profiling During Intervertebral Disc Development And Ageing.

Caldeira Joana J Santa Cátia C Osório Hugo H Molinos Maria M Manadas Bruno B Gonçalves Raquel R Barbosa Mário M

Scientific reports 20170914 1

Intervertebral disc (IVD) degeneration is often the cause of low back pain. Degeneration occurs with age and is accompanied by extracellular matrix (ECM) depletion, culminating in nucleus pulpous (NP) extrusion and IVD destruction. The changes that occur in the disc with age have been under investigation. However, a thorough study of ECM profiling is needed, to better understand IVD development and age-associated degeneration. As so, iTRAQ LC-MS/MS analysis of foetus, young and old bovine NPs, w ...[more]

PMID: 28912585

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Project description:Objective: Aging and early degeneration of the intervertebral disc (IVD) involves the substition of notochordal cells (NCs) in the nucleus pulposus (NP) by chondrocyte-like cells (CLCs). This study investigated the gene expression profiles involved in this process using NP tissue from both non-chondrodystrophic and chondrodystrophic dogs, a species with naturally occuring IVD degeneration. Methods: Dual channel DNA microarrays were used to compare 1) healthy NP tissue, 2) NP tissue with a mixed population of NCs and CLCs, and 3) NP tissue containing solely CLCs. Canonical Wnt-signaling was validated using qPCR of relevant Wnt target genes. Caveolin-1, a known regulator of canonical Wnt signaling, was investigated further in tissue sections using qPCR and immunohistochemistry, and in cultured NCs by qPCR and immunofluorescence. Also, the NP of 3-month-old caveolin-1 knock-out mice was histopathologically evaluated and compared with wild type mice of the same age. Results: Early IVD degeneration involved significant regulations in numerous pathways, such as extracellular matrix remodeling, Bone Morphogenetic Protein- , and Wnt/beta-catenin-signaling. With regard to Wnt/beta-catenin signaling, axin2 gene expression was significantly higher in chondrodystrophic dogs compared with non-chondrodystrophic dogs. IVD degeneration involved significant downregulation of axin2 gene expression and caveolin-1 gene and protein expression. NCs showed abundant caveolin-1 expression in vivo and in vitro, whereas CLCs did not. The NP of 3-month-old WT mice were rich in viable NCs, whereas the NPs of 3-month-old caveolin-1 knock-out mice contained chondroid-like matrix with small, rounded cells, the majority of which showed morphological signs of apoptosis. Conclusions: Aging and the onset of degeneration of the IVD involve significant downregulation of canonical Wnt signaling and caveolin-1, which appears to be essential in the physiology and preservation of NCs. DNA microarrays were used to compare nucleus palposus (NP) tissue of healthy and chondrodystrophic individuals. Furthermore, the situation of the tissue was divided into three stages: NCR: notochordal cell(NC) rich; CR: tissue containing solely chondrocyte-like-cells (CLC) and T: tissue with a mixed population of NCs and CLCs. Comparisons were analysed on a 2-color platform against a common reference sample, consisting of a multitude of canine organs, including liver, spleen, kidney, lung, hart, intestine and bone.

			Action	DRS
	Chondroitinase.group	Other
	Chondroitinase.wiff	Wiff
	Chondroitinase.wiff.scan	Wiff
	Chondroitinase_100.group	Other
	Chondroitinase_100.wiff	Wiff