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Sdc4 deletion perturbs intervertebral disc matrix homeostasis and promotes early osteopenia in the aging mouse spine

ABSTRACT: Sdc4 deletion perturbs intervertebral disc matrix homeostasis and promotes early osteopenia in the aging mouse spine

PROVIDER: PRJNA1018948 | ENA |

REPOSITORIES: ENA

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Sdc4 deletion perturbs intervertebral disc matrix homeostasis and promotes early osteopenia in the aging mouse spine

Project description:Transcriptional analysis of 6-month-old primary nucleus pulposus (NP) mouse disc tissues from wild-type (WT) and SDC4 KO mice, which harbor deletions of exon 2 to part of exon 5 that endcodes the N-terminal coding region. Breeder mice were provided by Dr. Michael Simons. SDC4's regulation of cytokine-dependent activation of the aggrecanse ADAMTS-5 is linked with inflammation-associated intervertebral disc degeneration. In this study, we aim to establish the role of SDC4 in matrix homeostasis under the context of aging.

2024-09-01 | GSE243573 | GEO

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Project description:Intervertebral disc degeneration

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Increased HIF-2α Activity in the Nucleus Pulposus Causes Mild Degenerative Changes in the Intervertebral Disc in the Aging Mouse Spine

Project description:Transcriptomic analysis of nucleus pulposus (NP) tissues from intervertebral discs of 14- and 24-month-old mice with the conditional postnatal overexpression of HIF-2α. Hypoxia-inducible factors (HIFs) are essential for the homeostasis of the hypoxic tissues, and therefore, increased activity of the transcription factor HIF-2α is shown to contribute to the pathogenesis of mild disc degeneration in the spine. We examined the transcriptomic profiles of nucleus pulposus cells in control and K19-HIF-2α-dPA overexpression mice using microarrays.

2024-03-27 | GSE249908 | GEO

Lactate Efflux From Intervertebral Disc Cells Is Required for Maintenance of Spine Health

Project description:Monocarboxylate Transporter 4 (MCT4) is important for H+/lactate efflux from nucleus pulposus cells in the intervertebral disc of mice. We examined the transcriptomic profile of nucleus pulposus cells in wild-type and MCT4 global knock-out mice using microarrays.

2020-05-15 | GSE130561 | GEO

The degradome of the human intervertebral disc

Project description:The intervertebral disc (IVD) is a joint in the spine that facilitates daily physical activity, comprising of the central nucleus pulposus (NP), surrounded by the annulus fibrosus (AF) and sandwiched between two cartilage endplates that function together as a unit. Changes to the IVD occur with aging, most drastically in the NP where it experiences dehydration and loss of cellularity, directly impacting on the integrity of the biomechanical functions of the IVD. We were interested in examining the types of degraded proteins in young and aged disc samples to further understand the protein turnover in aging and homeostasis. We analysed the degradome for degraded proteins using terminal amine isotopic labeling of substrates (TAILS) Clinical specimens from spine surgeries for scoliosis (young samples, n=3) or degeneration (aged samples, n=3) were used in this study.

2021-01-29 | PXD018298 | Pride

Actively synthesised proteins in human intervertebral disc

Project description:The intervertebral disc (IVD) is a joint in the spine that facilitates daily movement, comprising of the central nucleus pulposus (NP), surrounded by the annulus fibrosus (AF) and sandwiched between two cartilage endplates that function together as a unit. Changes to the IVD occur with aging, most drastically in the NP where it experiences dehydration and loss of cellularity, directly impacting on the integrity of the biomechanical functions of the IVD. Whilst the static proteome reflects the long-term accumulation of proteins and their turnover over the lifetime of the IVD, this information may not reflect immediate cellular changes that may alter during the course of time. To gain a better understanding of cellular function and protein turnover in disc homeostasis (health) versus aging, we analysed the actively synthesized proteins using the SILAC approach. Clinical specimens from spine surgeries for scoliosis (young samples; NP n=2, AF n=4) or degeneration (aged samples; NP n=1, AF n=1) were used in this study.

2021-01-29 | PXD018193 | Pride

Lactate Efflux From Intervertebral Disc Cells Is Required for Maintenance of Spine Health

Project description:Lactate Efflux From Intervertebral Disc Cells Is Required for Maintenance of Spine Health

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Proteomics for patients with intervertebral disc degeneration

Project description:Proteomics for patients with intervertebral disc degeneration

2024-04-10 | PXD051351 |

Proteomic landscape of murine intervertebral disc reveals mechanisms involved in homeostasis and disc structure maintenance

Project description:To fully apprehend the complex mechanisms responsible for intervertebral disc (IVD) degeneration, one needs to gain a deeper understanding of what characterizes a healthy disc. Using a quantitative proteomic approach, we analyzed methodically the differences existing between IVD genders, levels and components. A total of 2776 proteins were identified and we showed that cross regional but not gender variation existed along the mouse spine. Components comparison established CD109, CD81 and Col12a1 as novel NP and AF markers. NP cell clustering involved Cdh2 and tight junctions whereas early phase of adaptation to hypertonicity, the regulation of cell volume, was ensured by Slc12a2 and Wnk1. AF cells were protected from oxidative stress by expressing Atox1 and Sod3. Finally notochordal-like cells vacuoles were not acidic nor lipid droplets. Altogether, our study provides a first comprehensive landscape of the biology of a healthy murine IVD and identifies mechanisms involved in homeostasis and structure maintenance.

2021-09-07 | PXD006671 | Pride

Abcc6 null mice a model mineralization disorder PXE show vertebral osteopenia without enhanced intervertebral disc calcification with aging

Project description:Transcriptomic analysis of annulus fibrosus (AF) tissues from intervertebral discs of 7-month-old mice with the global deletion of ABCC6. ABCC6 is an efflux transporter of ATP in hepatic cells and loss of function results in metabolic ectopic mineralization disorder pseudoxanthoma elsaticum. To understand the role of ABCC6 and ectopic mineralization in the disc, we examined the transcriptomic profiles of annulus fibrosus cells in control and ABCC6 knock-out mice using microarrays.

2021-11-17 | GSE188943 | GEO

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