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Genetic background and aging-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice

ABSTRACT: Genetic background and aging-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice

PROVIDER: PRJNA1060319 | ENA |

REPOSITORIES: ENA

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Genetic background and aging-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice

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Genetic background and aging-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice

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Genetic background and aging-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice

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TMT-based proteomic analysis of CSF in dogs with intervertebral disc herniation

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Circulating Tenascin-C/-miR-155-5p identified as promising prognostic candidates of intervertebral disc herniation

Project description:Intervertebral disc (IVD) herniation is a complex and multifactorial condition with challenging diagnosis and limited therapeutic options, highlighting the need for reliable biomarkers to improve clinical decision-making. The aim of this study was to identify circulating prognostic biomarkers of IVD herniation regression. The plasma proteomic profile and the expression of circulating non-coding RNAs wereas analysed in a rat model ofs subjected to IVD herniation and proteomic and miRNA levels were correlated to herni-ation size. Four candidate proteins were identified (TNC, COPS3, JUP, GNAI2) that were significantly correlated with herniation size, with TNC further validated by ELISA. Additionally, miR-143-3p, miR-10b-5p, miR-27a-3p, miR-140-5p, miR-155-5p, miR-146a-5p and miR-21-5p were positively correlated with herniation size. Moreover, TNC, COPS3, JUP and GNAI2 were found to be potentiala targets of miR-155-5p. TNC-miR-155-5p pro-tein-miRNA pair standout as promising candidates to be part of a putative regulatory module worth investigating as a prognostic tool. This study provides the first combined proteomic and miRNAs account of preclinical plasma biomarkers of IVD herniation size, where TNC-miR-155-5p emerge as promising elements of a regulatory module with IVD herniation prognostic potential.

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Project description:Herniation of the intervertebral disc (IVDH) is the most common cause of neurological and intervertebral disc degeneration-related diseases. Since the disc starts to degenerate before it can be observed by currently available diagnostic methods, there is an urgent need for novel diagnostic approaches. To identify molecular networks and pathways which may play important roles in intervertebral disc herniation, as well as to reveal the potential features which could be useful for monitoring disease progression and prognosis, multi-omics profiling including high-resolution LC-MS-based metabolomics and proteomics was performed. Furthermore, multi-omics data were integrated to decipher a complex interaction between individual omic layers leading to improved prediction model. Together with metabolic pathways related to amino acids and lipid metabolism, and coagulation cascades, our integromics prediction model identified the key features in IVDH, namely the proteins FSTL1, SCG5, NUCB1 and CRSP2 and the metabolites N-acetyl-D-glucosamine and adenine, involved in neuropathic pain, myelination, neurotransmission and inflammatory response, respectively. Their clinical application is to be further investigated. The utilization of novel integrative interdisciplinary strategy may provide opportunities to apply the innovative diagnostic and monitoring methods for degenerative spinal disorders.

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SM/J mice display spontaneous early onset disc degeneration link to ion transport system and matrisome changes

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 good and bad intervertebral disc. Using a quantitative proteomic approach, we compared methodically the differences existing between a mouse model known as good healer LG/J to another mouse model characterize as bad healer SM/J. A total of 5245 proteins were identified. By assessing the overlap of the NP LG/J and SM/J proteomic signature with a list of over 1000 matrisomal proteins generated by Naba and co-workers (33), we provide a first comprehensive comparison of NP IVD matrix composition in a good and bad condition and identify potential changes that are fundamental for maintenance of a healthy disc.

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Project description:Lumbar intervertebral disc mRNA sequencing identifies the regulatory pathway in patients with disc herniation and spondylolisthesis

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Convergent Transcriptomic Signatures in Blood Link Lumbar Disc Herniation and Cervical Artery Dissection in Young Adults

Project description:Recurrent lumbar disc herniation (rLDH) and cervical artery dissection (CeAD) are significant neurological manifestations of undifferentiated connective tissue dysplasia (UCTD) in young adults. Molecular and histopathological evidence points to impaired cellular differentiation and aberrant extracellular matrix organization in these patients. Nevertheless, the pathogenic mechanisms of UCTD and the basis for its clinical heterogeneity remain largely unknown. Here, we conducted the first comparative transcriptome-wide analysis of peripheral blood mRNA in two UCTD cohorts—19 patients with CeAD and 12 with rLDH—alongside 18 healthy volunteers. Both UCTD cohorts exhibited common transcriptomic signatures indicating suppressed translation and RNA processing, mitochondrial dysfunction, and premature cellular senescence. Notably, the activated compensatory pathways, functionally annotated to small GTPase signaling, diverged between the cohorts. The rLDH group displayed a transcriptional signature of generalized extracellular matrix reorganization, whereas the CeAD cohort showed alterations primarily involved in cellular differentiation, adhesion, migration, and intercellular communication. Further differential analysis of upstream regulatory genes and splicing variants, complemented by single-cell RNA sequencing of tissue biopsies, is warranted to elucidate the precise mechanisms that drive the clinical heterogeneity of UCTD within the context of a potential sporadic ribosomopathy.

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