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:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS-derived intervertebral disc transcriptome profiling (RNA-seq) to microarray and quantitative reverse transcription polymerase chain reaction (qRT–PCR) methods and to evaluate protocols for optimal high-throughput data analysis
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS-derived intervertebral disc transcriptome profiling (RNA-seq) to microarray and quantitative reverse transcription polymerase chain reaction (qRT–PCR) methods and to evaluate protocols for optimal high-throughput data analysis
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.
Project description:Intervertebral disc degeneration is the main cause of low back pain and the mechanism of which is far from fully revealed. Although multiple factors are related to the intervertebral disc degeneration, inflammation and matrix metabolism dysregulation are the two key factors that play an important role in degeneration. Here, we found that CHSY3 is highly related to the nucleus pulposus degeneration. We generated CHSY3 knockout mice using Crisper/Cas9 system, and the NP cells are studied in this experiment.
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:Transcriptional analysis of 6-month-old primary nucleus pulposus (NP) and annulus fibrosus (AF) mouse disc tissues from wild-type (WT) and N153S mice, which harbor a mutation wich constiuitively activates Sting. Mouse details available here: https://www.jax.org/strain/033543 The cGAS-STING pathway promotes the senescence-associated secretory phenotype (SASP), which is associated with intervertebral disc degeneration, and has had implications in inflammatory musculoskeletal disorders. We examined the role of STING in the disc by examining the transcriptomic profiles of nucleus pulposus and annulus fibrosus cells in WT and N153S mice using microarray.
Project description:Transcriptional analysis of 24-month-old primary nucleus pulposus (NP) and annulus fibrosus (AF) mouse disc tissues from Sirt6fl/fl and Sirt6cKO mice, which harbor a mutation which constiuitively deletes Sirtuin 6 in aggrecan expressing cells. SIRT6 loss causes intervertebral disc degeneration in mice by dysregulating senescence and SASP status
