Project description:Intervertebral disc degeneration (IDD) leads to low back pain and disability globally. The pathophysiology of IDD is not entirely understood. There is increasing evidence that long noncoding RNAs (lncRNAs) play a key regulatory role in a wide range of biological processes. The purpose of this study was to comprehensively lncRNA and mRNA expression profiles of human intervertebral disc (IVD) tissues, specifically nucleus pulpous (NP) tissues, with early and advanced stages of disc degeneration. The overview of lncRNA and mRNA expression profiles in the current study revealed that differentially expressed lncRNAs and mRNAs were identified that have been reported to be relevant to IDD. Importantly, differentially expressed lncRNAs and mRNAs that regulate the major signaling pathways, such as NF-κB, MAPK, and Wnt signaling, that are well known to be responsible for the pathogenesis of IDD.
Project description:This study employs 10x Genomics single-cell RNA sequencing (scRNA-seq) to profile cellular changes within the intervertebral discs of diabetic mice. Diabetes mellitus is a systemic inflammatory disease known to drive pathological alterations in multiple organ systems. Here, we specifically investigate the process of diabetes-induced intervertebral disc degeneration. Our findings aim to provide novel insights into the pathogenic mechanisms underlying disc degeneration.
Project description:Disc Degeneration is a multifactorial disease which cause severe constant chronic pain. The development of disc degeneration could involve both genetic and environmental factors, so it's important to elucidate the difference in gene expression profiles between degenerative and non-degenerative discs from elderly patients and younger patients, respectively. Affymetrix GeneChip Human Genome U133A Array was used to derive gene expression profiles and identified genes that would express at significantly different levels between degenerative and non-degenerative samples. Human intervertebral disc tissues were harvested from elderly and younger patients with degenerative disc disease and adolescent idiopathic scoliosis, respectively, for RNA extraction and hybridization on Affymetrix microarrays. One degenerative sample was compared to one non-degenerative sample in the same microarray run, and comparative analyses were performed in triplicate. Gene whose expression levels varied across the samples with a log ratio >0.5 or <-0.5 were selected as the genes related to disc degeneration.
Project description:Lactate accumulation is a hallmark and contributing factor of intervertebral disc degeneration (IVDD). Lactate accumulation facilitates protein lactylation, while the role and mechanism of protein lactylation in IVDD remain unclear. In this study, we performed sequencing of the lactylation sites of whole protein in nucleus pulposus tissues of 3 normal and 3 acupuncture induced intervertebral disc degeneration rats to explore the function of different lactylation sites and their effects on intervertebral disc degeneration.
Project description:Failure of intervertebral disc components, e.g. the nucleus pulposus causes intervertebral disc disease and associated low-back pain. Despite the high prevalence of disc disease, the changes in intervertebral disc cells and their regenerative potential with ageing and degeneration are not fully elucidated. Understanding the cell lineage, cell differentiation and maintenance of nucleus pulposus may have therapeutic application for the regeneration of degenerative disc, with significant impact for healthy ageing. Here we found that TAGLN expressing cells are present in human healthy nucleus pulposus, but diminish in degenerative disc. By lineage analyses in mice, we found cells in the nucleus pulposus are derived from a peripherally located population of notochord-derived Tagln expressing cells (PeriNP cells). The PeriNP cells are proliferative and can differentiate into the inner part of the nucleus pulposus. The Tagln+ cells and descendants diminish during aging and puncture induced disc degeneration. The maintenance and differentiation of PeriNP cells is partially regulated by Smad4 dependent signaling. Removal of Smad4 by nucleus pulposus specific Cre (Foxa2mNE-Cre), results in decreased Tagln+ cells and abnormal disc morphology, leading to disc degeneration. Our findings propose that the PeriNP Tagln expressing cells are a pool of notochord-derived progenitors that are important for maintenance of the nucleus pulposus and provide insights for regenerative therapy against intervertebral disc degeneration.
Project description:Genetic background is a major determinant of disc degeneration, a leading cause of chronic back pain and disability. Herein, we demonstrate that premature disc cell senescence contributes to early-onset degeneration in SM/J mice and test two systemic senotherapeutic strategies to mitigate it: Navitoclax (Nav.) and a cocktail of Dasatinib and Quercetin (DQ). While Nav. treatment did not improve severe degeneration in SM/J mice, DQ-treated mice showed lower grades of degeneration and decreased levels of senescence markers p19ARF and p21. DQ promoted disc cell viability, phenotype retention, and limited fibrotic remodeling of the NP tissue. Transcriptomic analysis showed disc compartment-specific effects of the treatment, but cell cycle regulation and JNK signaling were commonly affected across tissue types. Additionally, comparison with previously reported C57BL/6N mice treated with DQ identified Junb and Zfp36l1 signaling as targets of DQ ameliorating intervertebral disc degeneration in mice. This study reinforces the positive role of senolytic treatments in mediating local senescence and intervertebral disc fibrosis. Moreover, these findings suggest that Junb and Zfp36l1 are mediators of this effect.
