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A potential target gene CD63 for different degrees of intervertebral disc degeneration.

ABSTRACT: Understanding molecular mechanisms of intervertebral disc degeneration (IDD) and providing a novel target for the treatment of IDD have important implications. We sought to explore a new promising gene target for the treatment of IDD. This study integrated 19,678 genes of 38 IDD patients from two gene datasets. Differentially Expressed Genes (DEGs) of annulus fibrosus were analyzed in groups with mild disc degeneration (MDD) and severe disc degeneration (SDD). We screened the hub gene through biological information technology (bioinformatic) methods. Then, we further validated the hub gene using annulus fibrosus and nucleus pulposus tissues from 12 patients with qRT-PCR. In addition, we explored its underlying molecular mechanism with GO, KEGG and GSEA. Through multiple screening bioinformatics methods, the hub gene CD63 was identified. The qRT-PCR explored that CD63 decreased significantly in SDD group compared to that in MDD group (P < 0.001). The GO, KEGG and GSEA of CD63 explored significant enrichment of the molecular features (P < 0.001), including the cellular component (Extracellular matrix, P < 0.001), the molecular function (collagen binding, P < 0.001), the biological processes (protein targeting, collagen fibril organization and platelet degranulation, P < 0.001) and the signaling pathways. Our research explored and validated a new regulatory gene, CD63 for different degrees of IDD. A new novel form of therapeutic target for IDD may be developed.

SUBMITTER: Gao S

PROVIDER: S-EPMC8770635 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Optineurin-mediated mitophagy as a potential therapeutic target for intervertebral disc degeneration.

Project description:Low back pain is thought to be mainly caused by intervertebral disc degeneration (IVDD), and there is a lack of effective treatments. Cellular senescence and matrix degradation are important factors that cause disc degeneration. Mitochondrial dysfunction induced by oxidative stress is an important mechanism of cellular senescence and matrix degradation in the nucleus pulposus (NP), and mitophagy can effectively remove damaged mitochondria, restore mitochondrial homeostasis, and mitigate the damage caused by oxidative stress. Optineurin (OPTN) is a selective mitophagy receptor, and its role in intervertebral disc degeneration remains unclear. Here, we aimed to explore the effect of OPTN on H2O2-induced nucleus pulposus cell (NPCs) senescence and matrix degradation in a rat model of disc degeneration. Western blot analysis showed that OPTN expression was reduced in degenerative human and rat nucleus pulposus tissues and increased in H2O2-induced senescent NPCs. OPTN overexpression significantly inhibited H2O2-induced senescence and increased matrix-associated protein expression in NPCs, but OPTN knockdown showed the opposite effect. As previous reports have suggested that mitophagy significantly reduces mitochondrial damage and reactive oxygen species (ROS) caused by oxidative stress, and we used the mitophagy agonist CCCP, the mitophagy inhibitor cyclosporin A (CsA), and the mitochondrial ROS (mtROS) scavenger mitoTEMPO and confirmed that OPTN attenuated NPCs senescence and matrix degeneration caused by oxidative stress by promoting mitophagy to scavenge damaged mitochondria and excess reactive oxygen species, thereby slowing the progression of IVDD. In conclusion, our research suggests that OPTN is involved in IVDD and exerts beneficial effects against IVDD.

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Project description:This SuperSeries is composed of the SubSeries listed below.

2024-04-05 | GSE230809 | GEO

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Project description:Intervertebral disc degeneration describes the vicious cycle of the deterioration of intervertebral discs and can eventually result in degenerative disc disease (DDD), which is accompanied by low-back pain, the musculoskeletal disorder with the largest socioeconomic impact world-wide. In more severe stages, intervertebral disc degeneration is accompanied by loss of joint space, subchondral sclerosis, and osteophytes, similar to osteoarthritis (OA) in the articular joint. Inspired by this resemblance, we investigated the analogy between human intervertebral discs and articular joints. Although embryonic origin and anatomy suggest substantial differences between the two types of joint, some features of cell physiology and extracellular matrix in the nucleus pulposus and articular cartilage share numerous parallels. Moreover, there are great similarities in the response to mechanical loading and the matrix-degrading factors involved in the cascade of degeneration in both tissues. This suggests that the local environment of the cell is more important to its behavior than embryonic origin. Nevertheless, OA is widely regarded as a true disease, while intervertebral disc degeneration is often regarded as a radiological finding and DDD is undervalued as a cause of chronic low-back pain by clinicians, patients and society. Emphasizing the similarities rather than the differences between the two diseases may create more awareness in the clinic, improve diagnostics in DDD, and provide cross-fertilization of clinicians and scientists involved in both intervertebral disc degeneration and OA.

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Gene expression profile analysis of human intervertebral disc degeneration.

Project description:In this study, we used microarray analysis to investigate the biogenesis and progression of intervertebral disc degeneration. The gene expression profiles of 37 disc tissue samples obtained from patients with herniated discs and degenerative disc disease collected by the National Cancer Institute Cooperative Tissue Network were analyzed. Differentially expressed genes between more and less degenerated discs were identified by significant analysis of microarray. A total of 555 genes were significantly overexpressed in more degenerated discs with a false discovery rate of < 3%. Functional annotation showed that these genes were significantly associated with membrane-bound vesicles, calcium ion binding and extracellular matrix. Protein-protein interaction analysis showed that these genes, including previously reported genes such as fibronectin, COL2A1 and β-catenin, may play key roles in disc degeneration. Unsupervised clustering indicated that the widely used morphology-based Thompson grading system was only marginally associated with the molecular classification of intervertebral disc degeneration. These findings indicate that detailed, systematic gene analysis may be a useful way of studying the biology of intervertebral disc degeneration.

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Project description:Intervertebral disc degeneration (IDD) causes a variety of signs and symptoms, such as low back pain (LBP), intervertebral disc herniation, and spinal stenosis, which contribute to high social and economic costs. IDD results from many factors, including genetic factors, aging, mechanical injury, malnutrition, and so on. The pathological changes of IDD are mainly composed of the senescence and apoptosis of nucleus pulposus cells (NPCs), the progressive degeneration of extracellular matrix (ECM), the fibrosis of annulus fibrosus (AF), and the inflammatory response. At present, IDD can be treated by conservative treatment and surgical treatment based on patients' symptoms. However, all of these can only release the pain but cannot reverse IDD and reconstruct the mechanical function of the spine. The latest research is moving towards the field of biotherapy. Mesenchymal stem cells (MSCs) are regard as the potential therapy of IDD because of their ability to self-renew and differentiate into a variety of tissues. Moreover, the non-coding RNAs (ncRNAs) are found to regulate many vital processes in IDD. There have been many successes in the in vitro and animal studies of using biotherapy to treat IDD, but how to transform the experimental data to real therapy which can apply to humans is still a challenge. This article mainly reviews the treatment strategies and research progress of IDD and indicates that there are many problems that need to be solved if the new biotherapy is to be applied to clinical treatment of IDD. This will provide reference and guidance for clinical treatment and research direction of IDD.

| S-EPMC9251272 | biostudies-literature

Macrophages and Intervertebral Disc Degeneration.

Project description:The intervertebral disc (IVD) aids in motion and acts to absorb energy transmitted to the spine. With little inherent regenerative capacity, degeneration of the intervertebral disc results in intervertebral disc disease, which contributes to low back pain and significant disability in many individuals. Increasing evidence suggests that IVD degeneration is a disease of the whole joint that is associated with significant inflammation. Moreover, studies show elevated macrophage accumulation within the IVD with increasing levels of disease severity; however, we still need to understand the roles, be they causative or consequential, of macrophages during the degenerative process. In this narrative review, we discuss hallmarks of IVD degeneration, showcase evidence of macrophage involvement during disc degeneration, and explore burgeoning research aimed at understanding the molecular pathways regulating macrophage functions during intervertebral disc degeneration.

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Different phylotypes of Cutibacterium acnes cause different modic changes in intervertebral disc degeneration.

Project description:BackgroundThe contribution of Cutibacterium acnes (C. acnes) infection to intervertebral disc degeneration (IDD) and the antibiotic therapy has evoked several controversies in recent years. While some microbiology studies report bacterial disc infection within IDD patients, others attribute the positive results to contamination during prolonged cultures. In addition to the clinical controversy, little was known about the mechanism of C. acnes-caused Modic changes (MCs) if C. acnes was the pathogenic factor.ObjectivesThis study aimed to investigate the inflammatory mechanism of MCs induced by different phylotypes of C. acnes in patients with IDD.MethodsSpecimens from sixty patients undergoing microdiscectomy for disc herniation were included, C. acnes were identified by anaerobic culture, followed by biochemical and PCR-based methods. The identified species of C. acnes were respectively inoculated into the intervertebral discs of rabbits. MRI and histological change were observed. Additionally, we detected MMP expression in the rabbit model using reverse transcription-quantitative polymerase chain reaction (RT-qPCR).ResultsOf the 60 cases, 18 (30%) specimens were positive for C. acnes, and we identified 4 of 6 defined phylogroups: IA, IB, II and III. The rabbits that received Type IB or II strains of C. acnes showed significantly decreased T1WI and higher T2WI at eighth weeks, while strain III C. acnes resulted in hypointense signals on both T1WI and T2WI. Histological examination results showed that all of the three types of C. acnes could cause disc degeneration and endplates rupture. Moreover, endplate degeneration induced by type IB or II strains of C. acnes is related with MMP13 expression. Meanwhile, strain III C. acnes might upregulated the level of MMP3.ConclusionThis study suggested that C. acnes is widespread in herniated disc tissues. Different types of C. acnes could induce different MCs by increasing MMP expression.

| S-EPMC9275720 | biostudies-literature

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