Current status and development direction of immunomodulatory therapy for intervertebral disk degeneration

Gao, Yanbing; Chen, Xiyue; Zheng, Guan; Lin, Maoqiang; Zhou, Haiyu; Zhang, Xiaobo

doi:10.3389/fmed.2023.1289642

Cited by 2 publications

(1 citation statement)

References 148 publications

(159 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Developing a more effective model to induce IDD would hasten the currently prolonged periods of time required for IDD progression, thereby reducing model time and costs. Furthermore, identifying and suppressing this immune response could also be used to decrease the development and progression of IDD in patients affected by the condition ( 31 , 42 , 43 ).…”

Section: Discussionmentioning

confidence: 99%

Immunization against nucleus pulposus antigens to accelerate degenerative disc disease in a rabbit model

Bonilla,

Sikes,

Burton

et al. 2024

Front. Vet. Sci.

View full text Add to dashboard Cite

Low back pain poses a significant societal burden, with progressive intervertebral disc degeneration (IDD) emerging as a pivotal contributor to chronic pain. Improved animal models of progressive IDD are needed to comprehensively investigate new diagnostic and therapeutic approaches to managing IDD. Recent studies underscore the immune system’s involvement in IDD, particularly with regards to the role of immune privileged tissues such as the nucleus pulposus (NP) becoming an immune targeting following initial disc injury. We therefore hypothesized that generating an active immune response against NP antigens with an NP vaccine could significantly accelerate and refine an IDD animal model triggered by mechanical puncture of the disc. To address this question, rabbits were immunized against NP antigens following disc puncture, and the impact on development of progressive IDD was assessed radiographically, functionally, and histologically compared between vaccinated and non-vaccinated animals over a 12-week period. Immune responses to NP antigens were assessed by ELISA and Western blot. We found that the vaccine elicited strong immune responses against NP antigens, including a dominant ~37 kD antigen. Histologic evaluation revealed increases IDD in animals that received the NP vaccine plus disc puncture, compared to disc puncture and vaccine only animals. Imaging evaluation evidenced a decrease in disc height index and higher scores of disc degeneration in animals after disc punctures and in those animals that received the NP vaccine in addition to disc puncture. These findings therefore indicate that it is possible to elicit immune responses against NP antigens in adult animals, and that these immune responses may contribute to accelerated development of IDD in a novel immune-induced and accelerated IDD model.

show abstract

Section: Discussionmentioning

confidence: 99%

Immunization against nucleus pulposus antigens to accelerate degenerative disc disease in a rabbit model

Bonilla,

Sikes,

Burton

et al. 2024

Front. Vet. Sci.

View full text Add to dashboard Cite

show abstract

Identification of cellular senescence-related genes and immune cell infiltration characteristics in intervertebral disc degeneration

Wang,

Wang

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

BackgroundIntervertebral disc degeneration (IDD) progression involves multiple factors, including loss of nucleus pulposus cells and extracellular matrix as the basic pathological mechanism of degeneration, and is closely related to cellular senescence and immune cell infiltration. The aim of study was to identify critical cellular senescence-related genes and immune cell infiltration characteristics in IDD.MethodsFour datasets, including GSE70362, GSE112216, GSE114169, and GSE150408, were downloaded from the Gene Expression Omnibus database. The senescence-related genes were acquired from the CellAge Database and intersected with differentially expressed genes (DEGs) between IDD and control samples for senescence-related DEGs (SRDEGs). Protein-protein interaction (PPI) network analysis was performed to obtain ten hub SRDEGs. A consensus cluster analysis based on these hub genes was performed to divide the patients into clusters. The functional enrichment, and immune infiltration statuses of the clusters were compared. Weighted gene co-expression network analysis was used to identified key gene modules. The overlapping genes from key modules, DEGs of clusters and hub SRDEGs were intersected to obtain potential biomarkers. To verify the expression of potential biomarkers, quantitative polymerase chain reaction (qPCR) and immunohistochemistry were performed by using human intervertebral disc tissues.ResultsIn the GSE70362 dataset, a total of 364 DEGs were identified, of which 150 were upregulated and 214 were downregulated, and 35 genes were selected as SRDEGs. PPI analysis revealed ten hub SRDEGs and consensus cluster analysis divided the patients into two clusters. Compared to Cluster 2, Cluster 1 was highly enriched in extracellular matrix organization and various metabolic process. The level of Follicular T helper cells in the Cluster 1 was significantly higher than that in the Cluster 2. IGFBP3 and NQO1 were identified as potential biomarkers. The remaining 3 datasets, and the result of qPCR and immunohistochemistry showed that the expression levels of NQO1 and IGFBP3 in the degenerated group were higher than those in the control or treatment groups.ConclusionSenescence-related genes play a key role in the development and occurrence of IDD. IGFBP3 and NQO1 are strongly correlated with immune infiltration in the IDD and could become novel therapeutic targets that prevent the progression of IDD.

show abstract

Current status and development direction of immunomodulatory therapy for intervertebral disk degeneration

Cited by 2 publications

References 148 publications

Immunization against nucleus pulposus antigens to accelerate degenerative disc disease in a rabbit model

Immunization against nucleus pulposus antigens to accelerate degenerative disc disease in a rabbit model

Identification of cellular senescence-related genes and immune cell infiltration characteristics in intervertebral disc degeneration

Contact Info

Product

Resources

About