Intradiscal injection of simvastatin retards progression of intervertebral disc degeneration induced by stab injury

Abstract Background Intervertebral disc degeneration (IVDD)-related disorders are the major causes of low back pain. A previous study suggested that Notch activation serves as a protective mechanism and is a part of the compensatory response that maintains the necessary resident nucleus pulposus (NP) cell proliferation to replace lost or non-functional cells. However, the exact mechanism remains to be determined. In this study, we aimed to investigate the role of JAG2/Notch2 in NP cell proliferation and apoptosis. Methods Recombinant JAG2 or Notch2, Hes1, and Hey2 siRNAs were used to activate or inhibit Notch signaling. Cell proliferation, apoptosis, cell cycle regulatory factors, and pathways associated with Notch-mediated proliferation were examined. In vivo experiments involving an intradiscal injection of Sprague-Dawley rats were performed. Results Recombinant JAG2 induced Notch2 and Hes1/Hey2 expression together with NP cell proliferation. Downregulation of Notch2/Hes1/Hey2 induced G0/G1 phase cell cycle arrest in NP cells. Moreover, Notch2 mediated NP cell proliferation by regulating cyclin D1 and by activating PI3K/Akt and Wnt/β-catenin signaling. Furthermore, Notch signaling inhibited TNF-α-promoted NP cell apoptosis by suppressing the formation of the RIP1-FADD-caspase-8 complex. Finally, we found that intradiscal injection of JAG2 alleviated IVDD and that sh-Notch2 aggravated IVDD in a rat model. These results indicated that JAG2/Notch2 inhibited IVDD by modulating cell proliferation, apoptosis, and extracellular matrix. The JAG2/Notch2 axis regulated NP cell proliferation via PI3K/Akt and Wnt/β-catenin signaling and inhibited TNF-α-induced apoptosis by suppressing the formation of the RIP1-FADD-caspase-8 complex. Conclusions The current and previous results shed light on the therapeutic implications of targeting the JAG2/Notch2 axis to inhibit or reverse IVDD.

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Safety of intradiscal injection and biocompatibility of polyester amide microspheres in a canine model predisposed to intervertebral disc degeneration

Journal of Biomedical Materials Research Part B Applied Biomaterials ◽

10.1002/jbm.b.33579 ◽

2015 ◽

Vol 105 (4) ◽

pp. 707-714 ◽

Cited By ~ 9

Author(s):

Nicole Willems ◽

George Mihov ◽

Guy C.M. Grinwis ◽

Maarten van Dijk ◽

Detlef Schumann ◽

...

Keyword(s):

Intervertebral Disc ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Canine Model ◽

Intradiscal Injection

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Effects of Intradiscal Injection of Local Anesthetics on Intervertebral Disc Degeneration in Rabbit Degenerated Intervertebral Disc

Journal of Orthopaedic Research® ◽

10.1002/jor.24347 ◽

2019 ◽

Vol 37 (9) ◽

pp. 1963-1971 ◽

Cited By ~ 1

Author(s):

Katsuro Ura ◽

Hideki Sudo ◽

Koji Iwasaki ◽

Takeru Tsujimoto ◽

Daisuke Ukeba ◽

...

Keyword(s):

Intervertebral Disc ◽

Disc Degeneration ◽

Local Anesthetics ◽

Intervertebral Disc Degeneration ◽

Intradiscal Injection

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MicroRNA-338-3p as a novel therapeutic target for intervertebral disc degeneration

Experimental & Molecular Medicine ◽

10.1038/s12276-021-00662-3 ◽

2021 ◽

Author(s):

Hua Jiang ◽

Abu Moro ◽

Jiaqi Wang ◽

Dihua Meng ◽

Xinli Zhan ◽

...

Keyword(s):

Intervertebral Disc ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Negative Regulator ◽

Erk Pathway ◽

Matrix Synthesis ◽

Functional Studies ◽

Promising Target ◽

Proliferation And Apoptosis ◽

Intradiscal Injection

AbstractRecent studies have demonstrated the pivotal role played by microRNAs (miRNAs) in the etiopathogenesis of intervertebral disc degeneration (IDD). The study of miRNA intervention in IDD models may promote the advancement of miRNA-based therapeutic strategies. The aim of the current study was to investigate whether intradiscal delivery of miRNA can attenuate IDD development. Our results showed that miR-338-3p expression was significantly increased in the nucleus pulposus (NP) of patients with IDD. Moreover, there was a statistically significant positive correlation between the expression level of miR-338-3p and the severity of IDD. Our functional studies showed that miR-338-3p significantly influenced the expression of extracellular matrix synthesis genes, as well as the proliferation and apoptosis of NP cells. Mechanistically, miR-338-3p aggravated IDD progression by directly targeting SIRT6, a negative regulator of the MAPK/ERK pathway. Intradiscal injection of antagomir-338-3p significantly decelerated IDD development in mouse models. Our study is the first to identify miR-338-3p as a mediator of IDD and thus may be a promising target for rescuing IDD.

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Faculty Opinions recommendation of Novel function of TWEAK in inducing intervertebral disc degeneration.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1095070.550070 ◽

2007 ◽

Author(s):

Helen Gruber

Keyword(s):

Intervertebral Disc ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration

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INTERVERTEBRAL DISC DEGENERATION LINKED TO STRUCTURAL GENE VARIATIONS

Pakistan Journal of Medicine and Dentistry ◽

10.36283/pjmd8-4/012 ◽

2019 ◽

Author(s):

Saeeda Baig

Keyword(s):

Intervertebral Disc ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

English Language ◽

Tandem Repeats ◽

Lumbar Disc ◽

Disease Process ◽

Nucleotide Polymorphisms ◽

Structural Protein ◽

Lumbar Disc Degeneration

During the recent past focus has shifted from identifying intervertebral disc degeneration as being caused by physical exposure and strain to being linked with a variety of genetic variations. The objective of this review is to provide an up to date review of the existing research data regarding the relation of intervertebral disc degeneration to structural protein genes and their polymorphisms and thus help clearly establish further avenues where research into causation and treatment is needed. A comprehensive search using the keywords “Collagen”, “COL”, “Aggrecan”, “AGC”, “IVDD”, “intervertebral disc degeneration”, and “lumbar disc degeneration” from PubMed and Google Scholar, where literature in the English language was selected spanning from 1991 to 2019. There are many genes involved in the production of structural components of an intervertebral disc. The issues in production of these components involve the over-expression or under-expression of their genes, and single nucleotide polymorphisms and variable number of tandem repeats affecting their structures. These structural genes include primarily the collagen and the aggrecan genes. While genetic and environmental factors all come into play with a disease process like disc degeneration, the bulk of research now shows the significantly larger impact of hereditary over exposure. While further research is needed into some of the lesser studied genes linked to IVDD and also the racial variations in genetic makeup, the focus in the near future should be on establishment of genetic testing to identify individuals at greater risk of disease and deliberation regarding the use of gene therapy to prevent disc degeneration.

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