Dataset Information

Global Spinal Cord Peptidome Profiling in Response to Osteoarthritis in Rats

ABSTRACT: Osteoarthritis (OA) is a complex and increasingly prevalent condition affecting an estimated 600 million people worldwide, significantly diminishing quality of life. Understanding OA as both an inflammatory and neurological disease presents challenges for treatment, with no approved disease-modifying therapies available. The neuroactive effects of OA pain on neuropeptide systems, particularly within the spinal cord, remain underexplored, impeding therapeutic advances. Here, we employed mass spectrometry (MS) to characterize the spinal cord peptidome in a validated rat model of OA pain. Peptidome was analyzed at different time points in the Montreal Induction of Rat Arthritis Testing (MI-RAT©; n = 20) model compared to arthrotomic group (Sham; n = 4) and healthy group (Naive; n = 9). Label-free peptidome profiling using liquid chromatography coupled with tandem MS (LC-MS/MS) revealed dynamic changes in endogenous peptides following OA progression, leading to the identification of 624 peptides derived from 29 prohormone precursors. Our findings indicate substantial changes in peptide levels in the spinal cord, particularly involving neuropeptide substance P and peptides derived from proenkephalin, calcitonin gene-related peptide, and somatostatin. These data offer novel insights into the molecular mechanisms underlying OA-associated pain and highlight potential targets for new therapeutic interventions to treat neurochronic pain conditions.

INSTRUMENT(S):

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Spinal Cord

DISEASE(S): Osteoarthritis

SUBMITTER: Gaoyuan Lu

LAB HEAD: Lingjun Li

PROVIDER: PXD060558 | Pride | 2025-10-28

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	220419_Rat_reviewed_SignalP6.fasta	Fasta
	GL_240321_Rat_SpinalCord_Neuropeptidome_S1.raw	Raw
	GL_240321_Rat_SpinalCord_Neuropeptidome_S10.raw	Raw
	GL_240321_Rat_SpinalCord_Neuropeptidome_S11.raw	Raw
	GL_240321_Rat_SpinalCord_Neuropeptidome_S12.raw	Raw

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Project description:We have investigated the process of disease-induced functional perturbation and the related transcriptional changes occurring in thoraco-lumbar spinal cord extracted from Sprague-Dawley rats heterozygous for the G93A SOD1 gene mutation (Emerging Model 2148 Het Male, Taconic USA; Wyeth and Amyotrophic Lateral Sclerosis Association 2002) using spinal cord from wild type females littermates as reference tissues. Rats were obtained from a breeding project at Taconic Breeding Services (USA). We have applied large-scale gene expression analysis to define the pattern or transcriptional changes occurring in spinal cord from the G93A SOD1 rat model from a pre-symptomatic stage, at disease onset and at end-stage disease, using Bead Array analysis (Illumina, San Diego, USA). We have pooled spinal cord from N:5 transgenic rats for each of the time points considered, using the same pools of spinal cord from sex and age-matched WT rats as reference. In this specific project, the aim was to obtain a gene ontology (GO) pathway analysis of the transcriptional changes induced by the G93A SOD1 mutation in rat spinal cord. Hence, we have opted for a sample pooling strategy, well aware that in so doing, we would not obtaineed information about individuals genes variation across the samples in study but an overall view of the activation of multi-genes molecular signals. Total RNA was isolated from the spinal cords of mutant (G93A SOD1 gene mutation) female rats sacrificed at a pre-symptomatic stage (10-week old), at disease onset and at end stage disease and from age and sex-matched wild type (WT) littermates. RNA samples obtained from spinal cord extracted from rats of the same genetic types and sacrificed at the same time points (e.g. 5 RNA samples from mutant spinal cord from end-stage rats; 5 RNA samples from mutant spinal cord from rats at disease onset; 5 RNA samples from mutant pre-symptomatic rats and 5 RNA samples from spinal cord obtained from age-matched WT rats sacrificed at each of the 3 time points) were pooled and used for gene expression analysis and Ontology analysis of the expression profiles.

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Global Spinal Cord Peptidome Profiling in Response to Osteoarthritis in Rats

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