Lovastatin prevents discography-associated degeneration and maintains the functional morphology of intervertebral discs

Ming Hsiao Hu, Kai Chiang Yang, Yeong Jang Chen, Yuan Hui Sun, Shu Hua Yang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background context Discography is an important diagnostic approach to identify the painful discs. However, the benefit of discography, a procedure involving needle puncture and injection of the diagnostic agent into the intervertebral disc, is controversial and has been reported to be associated with accelerated degeneration.

Purpose To investigate the effect of lovastatin on the prevention of degeneration caused by a discography simulation procedure in rat caudal discs.

Study design In vivo study using rat caudal discs.

Methods A single flexible 27-gauge needle puncture into rat caudal discs was performed under fluoroscopic monitoring. Different concentrations (0.1, 1, 5, and 10 μM) of lovastatin were prepared and injected into randomly chosen caudal discs. RNA expression of selected genes, histologic, and immunohistochemical staining were performed to evaluate the phenotypic effects of lovastatin on rat caudal discs.

Results Simulation of the discography procedure by puncturing the rat caudal discs with a 27-gauge needle and injection of saline solution induced degenerative changes in the nucleus pulposus with minimal damage to the annulus fibrosus. Aggrecan, Type II collagen, and SOX9 expressions were upregulated, whereas Type I collagen expression was significantly suppressed in discs treated with 5 and 10 μM lovastatin. Discs treated with 5 and 10 μM lovastatin were subjected to alcian blue staining and immunohistochemistry that revealed higher levels of glycosaminoglycans and an increase in the number of cells producing S-100 proteins, Type II collagen, and bone morphogenetic protein-2 (BMP-2), respectively. The most effective phenotypic repair was observed in discs treated with 10 μM lovastatin.

Conclusions Intradiscal administration of lovastatin solution upregulated the expressions of BMP-2 and SOX9 and promoted chondrogenesis of rat caudal discs after needle puncture and substance injection. Therefore, we suggest that lovastatin promotes disc repair and can be used as a potential therapeutic agent for biological repair of disc degeneration after the diagnostic discography procedure.

Original languageEnglish
Pages (from-to)2459-2466
Number of pages8
JournalSpine Journal
Volume14
Issue number10
DOIs
Publication statusPublished - Oct 1 2014

Fingerprint

Lovastatin
Intervertebral Disc
Needles
Punctures
Bone Morphogenetic Protein 2
Collagen Type II
Injections
Staining and Labeling
Aggrecans
Chondrogenesis
Intervertebral Disc Degeneration
Alcian Blue
S100 Proteins
Collagen Type I
Glycosaminoglycans
Sodium Chloride
Cell Count
Immunohistochemistry
RNA
Gene Expression

Keywords

  • Bone morphogenetic protein-2
  • Degeneration
  • Discography
  • Intervertebral disc
  • Lovastatin
  • Nucleus pulposus
  • SOX9

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery
  • Medicine(all)

Cite this

Lovastatin prevents discography-associated degeneration and maintains the functional morphology of intervertebral discs. / Hu, Ming Hsiao; Yang, Kai Chiang; Chen, Yeong Jang; Sun, Yuan Hui; Yang, Shu Hua.

In: Spine Journal, Vol. 14, No. 10, 01.10.2014, p. 2459-2466.

Research output: Contribution to journalArticle

Hu, Ming Hsiao ; Yang, Kai Chiang ; Chen, Yeong Jang ; Sun, Yuan Hui ; Yang, Shu Hua. / Lovastatin prevents discography-associated degeneration and maintains the functional morphology of intervertebral discs. In: Spine Journal. 2014 ; Vol. 14, No. 10. pp. 2459-2466.
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AU - Hu, Ming Hsiao

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AU - Yang, Shu Hua

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N2 - Background context Discography is an important diagnostic approach to identify the painful discs. However, the benefit of discography, a procedure involving needle puncture and injection of the diagnostic agent into the intervertebral disc, is controversial and has been reported to be associated with accelerated degeneration.Purpose To investigate the effect of lovastatin on the prevention of degeneration caused by a discography simulation procedure in rat caudal discs.Study design In vivo study using rat caudal discs.Methods A single flexible 27-gauge needle puncture into rat caudal discs was performed under fluoroscopic monitoring. Different concentrations (0.1, 1, 5, and 10 μM) of lovastatin were prepared and injected into randomly chosen caudal discs. RNA expression of selected genes, histologic, and immunohistochemical staining were performed to evaluate the phenotypic effects of lovastatin on rat caudal discs.Results Simulation of the discography procedure by puncturing the rat caudal discs with a 27-gauge needle and injection of saline solution induced degenerative changes in the nucleus pulposus with minimal damage to the annulus fibrosus. Aggrecan, Type II collagen, and SOX9 expressions were upregulated, whereas Type I collagen expression was significantly suppressed in discs treated with 5 and 10 μM lovastatin. Discs treated with 5 and 10 μM lovastatin were subjected to alcian blue staining and immunohistochemistry that revealed higher levels of glycosaminoglycans and an increase in the number of cells producing S-100 proteins, Type II collagen, and bone morphogenetic protein-2 (BMP-2), respectively. The most effective phenotypic repair was observed in discs treated with 10 μM lovastatin.Conclusions Intradiscal administration of lovastatin solution upregulated the expressions of BMP-2 and SOX9 and promoted chondrogenesis of rat caudal discs after needle puncture and substance injection. Therefore, we suggest that lovastatin promotes disc repair and can be used as a potential therapeutic agent for biological repair of disc degeneration after the diagnostic discography procedure.

AB - Background context Discography is an important diagnostic approach to identify the painful discs. However, the benefit of discography, a procedure involving needle puncture and injection of the diagnostic agent into the intervertebral disc, is controversial and has been reported to be associated with accelerated degeneration.Purpose To investigate the effect of lovastatin on the prevention of degeneration caused by a discography simulation procedure in rat caudal discs.Study design In vivo study using rat caudal discs.Methods A single flexible 27-gauge needle puncture into rat caudal discs was performed under fluoroscopic monitoring. Different concentrations (0.1, 1, 5, and 10 μM) of lovastatin were prepared and injected into randomly chosen caudal discs. RNA expression of selected genes, histologic, and immunohistochemical staining were performed to evaluate the phenotypic effects of lovastatin on rat caudal discs.Results Simulation of the discography procedure by puncturing the rat caudal discs with a 27-gauge needle and injection of saline solution induced degenerative changes in the nucleus pulposus with minimal damage to the annulus fibrosus. Aggrecan, Type II collagen, and SOX9 expressions were upregulated, whereas Type I collagen expression was significantly suppressed in discs treated with 5 and 10 μM lovastatin. Discs treated with 5 and 10 μM lovastatin were subjected to alcian blue staining and immunohistochemistry that revealed higher levels of glycosaminoglycans and an increase in the number of cells producing S-100 proteins, Type II collagen, and bone morphogenetic protein-2 (BMP-2), respectively. The most effective phenotypic repair was observed in discs treated with 10 μM lovastatin.Conclusions Intradiscal administration of lovastatin solution upregulated the expressions of BMP-2 and SOX9 and promoted chondrogenesis of rat caudal discs after needle puncture and substance injection. Therefore, we suggest that lovastatin promotes disc repair and can be used as a potential therapeutic agent for biological repair of disc degeneration after the diagnostic discography procedure.

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KW - Degeneration

KW - Discography

KW - Intervertebral disc

KW - Lovastatin

KW - Nucleus pulposus

KW - SOX9

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