Causes of and Molecular Targets for the Treatment of Intervertebral Disc Degeneration: A Review

Ohnishi, Takashi; Iwasaki, Norimasa; Sudo, Hideki

doi:10.3390/cells11030394

Cited by 63 publications

(67 citation statements)

References 146 publications

(302 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is a programmed cell death, also known as inflammatory necrosis, closely related to inflammation, immunity, and apoptosis [ 11 ]. Various studies have shown that pyroptosis plays a crucial role in IDD [ 12 , 13 ]. When NP cells (NPCs) undergo pyroptosis, the main manifestations are raised inflammatory factors, NLRP3, caspase-1, and other genes [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of SMIM1 and SEZ6L2 as Potential Biomarkers for Genes Associated with Intervertebral Disc Degeneration in Pyroptosis

et al. 2022

View full text Add to dashboard Cite

Background. Inflammatory reactions and pyroptosis play an important role in the pathology of intervertebral disc degeneration (IDD). The aim of the present study was to investigate pyroptosis in the nucleus pulposus cells (NPCs) of inflammatory induced IDD by bioinformatic methods and to search for possible diagnostic biomarkers. Methods. Gene expression profiles related to IDD were downloaded from the GEO database to identify differentially expressed genes (DEGs) between inflammation-induced IDD and non-inflammatory intervention samples. Pyroptosis genes were then searched for, and their expression in IDD was analyzed. Weighted gene co-expression network analysis (WGCNA) was then used to search for modules of IDD genes associated with pyroptosis and intersected with DEGs to discover candidate genes that would be diagnostically valuable. A LASSO model was developed to screen for genes that met the requirements, and ROC curves were created to clarify the diagnostic value of the genetic markers. Ultimately, the screened genes were further validated, and their diagnostic value assessed by selecting gene sets from the GEO database. RT-PCR was used to assess the mRNA expression of diagnostic markers in the nucleus pulposus (NP). Pan-cancer analysis was applied to demonstrate the expression and prognostic value of the screened genes in various tumors. Results. A total of 733 DEGs were identified in GSE41883 and GSE27494, which were mainly enriched in transmembrane receptor protein serine/threonine, kinase signaling pathway, response to lipopolysaccharide, and other biological processes, and they were mainly related to TGF beta signaling pathway, toll-like receptor signaling pathway, and TNF signaling pathway. A total of 81 genes related to pyroptosis were identified in the literature, and eight genes related to IDD were identified in the Veen diagram, namely, IL1A, IL1B, NOD2, GBP1, IL6, AK1, EEF2K, and PYCARD. Eleven candidate genes were obtained after locating the intersection of pyroptosis-related module genes and DEGs according to WGCNA analysis. A total of six valid genes were obtained after constructing a machine learning model, and five key genes were finally identified after correlation analysis. GSE23132 and GSE56081 validated the candidate genes, and the final IDD-related diagnostic markers were obtained as SMIM1 and SEZ6L2. RT-PCR results indicated that the mRNA expression of both was significantly elevated in IDD. The pan-cancer analysis demonstrated that SMIM1 and SEZ6L2 have important roles in the expression and prognosis of various tumors. Conclusion. In conclusion, this research identifies SMIM1 and SEZ6L2 as important biomarkers of IDD associated with pyroptosis, which will help to unravel the development and pathogenesis of IDD and determine potential therapeutic targets.

show abstract

Section: Introductionmentioning

confidence: 99%

Identification of SMIM1 and SEZ6L2 as Potential Biomarkers for Genes Associated with Intervertebral Disc Degeneration in Pyroptosis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The delicate balance between catabolism and anabolism is lost in IVD, and a series of degradation processes start and are facilitated by numerous factors (e.g., genetic and environmental changes) ( Ravichandran et al, 2022 ). There are some critical pathological changes during IVDD, consisting of abnormal synthesis and degradation of ECM, cellular senescence and death, increased angiogenesis and innervation, aging of AF, as well as calcification of CEP ( Ohnishi et al, 2022 ; Wang et al, 2020 ).…”

Section: Intervertebral Disc and Intervertebral Disc Degenerationmentioning

confidence: 99%

“…When NCs are gradually lost, and the dialogue with NPS cells ends, IVDD occurs ( Erwin et al, 2006 ). At the early stage of IVDD, the productions of aggrecan and type II collagen are inhibited, the water of hyaluronic acid polymerized into proteoglycan is lost, whereas the productions of type I collagen, fibronectin, and other proteoglycans are facilitated ( Ohnishi et al, 2022 ; Yee et al, 2016 ). This finding is correlated with an upregulated expression of matrix-degrading proteins (e.g., MMPs and ADAMTS).…”

Section: Intervertebral Disc and Intervertebral Disc Degenerationmentioning

confidence: 99%

Exosomes and exosomal miRNAs: A new therapy for intervertebral disc degeneration

Wu²,

Tan

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Low back pain has been found as a major cause of global disease burden and disability. Intervertebral disc degeneration is recognized as the vital factor causing low back pain. Intervertebral disc degeneration has a complex mechanism and cannot be avoided. Traditional strategies for the treatment of intervertebral disc degeneration cannot meet the needs of intervertebral disc regeneration, so novel treatment methods are urgently required. Exosomes refer to extracellular vesicles that can be released by most cells, and play major roles in intercellular material transport and information transmission. MicroRNAs have been identified as essential components in exosomes, which can be selectively ingested by exosomes and delivered to receptor cells for the regulation of the physiological activities and functions of receptor cells. Existing studies have progressively focused on the role of exosomes and exosomal microRNAs in the treatment of intervertebral disc degeneration. The focus on this paper is placed on the changes of microenvironment during intervertebral disc degeneration and the biogenesis and mechanism of action of exosomes and exosomal microRNAs. The research results and deficiencies of exosomes and exosomal microRNAs in the regulation of apoptosis, extracellular matrix homeostasis, inflammatory response, oxidative stress, and angiogenesis in intervertebral disc degeneration are primarily investigated. The aim of this paper is to identify the latest research results, potential applications and challenges of this emerging treatment strategy.

show abstract

“…Some IVDD patients benefit from conservative care, which includes physiotherapy, oral analgesics, vitamins, exercise, heat, cold, corsetry, acupuncture, radio frequency/shock waves, and varying intensities of massage [ 204 , 205 , 207 ]. However, the condition worsens for some patients or frequently recurs [ 208 ].…”

Section: Current Treatment Approaches For Ivddmentioning

confidence: 99%

Targeting Autophagy for Developing New Therapeutic Strategy in Intervertebral Disc Degeneration

et al. 2022

View full text Add to dashboard Cite

Intervertebral disc degeneration (IVDD) is a prevalent cause of low back pain. IVDD is characterized by abnormal expression of extracellular matrix components such as collagen and aggrecan. In addition, it results in dysfunctional growth, senescence, and death of intervertebral cells. The biological pathways involved in the development and progression of IVDD are not fully understood. Therefore, a better understanding of the molecular mechanisms underlying IVDD could aid in the development of strategies for prevention and treatment. Autophagy is a cellular process that removes damaged proteins and dysfunctional organelles, and its dysfunction is linked to a variety of diseases, including IVDD and osteoarthritis. In this review, we describe recent research findings on the role of autophagy in IVDD pathogenesis and highlight autophagy-targeting molecules which can be exploited to treat IVDD. Many studies exhibit that autophagy protects against and postpones disc degeneration. Further research is needed to determine whether autophagy is required for cell integrity in intervertebral discs and to establish autophagy as a viable therapeutic target for IVDD.

show abstract

Causes of and Molecular Targets for the Treatment of Intervertebral Disc Degeneration: A Review

Cited by 63 publications

References 146 publications

Identification of SMIM1 and SEZ6L2 as Potential Biomarkers for Genes Associated with Intervertebral Disc Degeneration in Pyroptosis

Identification of SMIM1 and SEZ6L2 as Potential Biomarkers for Genes Associated with Intervertebral Disc Degeneration in Pyroptosis

Exosomes and exosomal miRNAs: A new therapy for intervertebral disc degeneration

Targeting Autophagy for Developing New Therapeutic Strategy in Intervertebral Disc Degeneration

Contact Info

Product

Resources

About