Intradiscal injection of simvastatin results in radiologic, histologic, and genetic evidence of disc regeneration in a rat model of degenerative disc disease.
Spine J
; 14(6): 1017-28, 2014 Jun 01.
Article
in En
| MEDLINE
| ID: mdl-24291703
ABSTRACT
BACKGROUND CONTEXT A large percentage of back pain can be attributed to degeneration of the intervertebral disc (IVD). Bone morphogenetic protein 2 (BMP-2) is known to play an important role in chondrogenesis of the IVD. Simvastatin is known to upregulate expression of BMP-2. Thus, we hypothesized that intradiscal injection of simvastatin in a rat model of degenerative disc disease (DDD) would result in retardation of DDD. PURPOSE:
The purpose of the present study was to develop a novel conservative treatment for DDD and related discogenic back pain. STUDY DESIGN/SETTING:
The setting of this study is the laboratory investigation.METHODS:
Disc injury was induced in 272 rats via 21-ga needle puncture. After 6 weeks, injured discs were treated with simvastatin in a saline or hydrogel carrier. Rats were sacrificed at predetermined time points. Outcome measures assessed were radiologic, histologic, and genetic. Radiologically, the magnetic resonance imaging (MRI) index (number of pixels multiplied by the corresponding image densities) was determined. Histologically, disc spaces were read by three blinded scorers using a previously described histologic grading scale. Genetically, nuclei pulposi were harvested, and polymerase chain reaction was run to determine relative levels of aggrecan, collagen type II, and BMP-2 gene expression.RESULTS:
Radiologically, discs treated with 5 mg/mL of simvastatin in hydrogel or saline demonstrated MRI indices that were normal through 8 weeks after treatment, although this was more sustained when delivered in hydrogel. Histologically, discs treated with 5 mg/mL of simvastatin in hydrogel demonstrated improved grades compared with discs treated at higher doses. Genetically, discs treated with 5 mg/mL of simvastatin in hydrogel demonstrated higher gene expression of aggrecan and collagen type II than control.CONCLUSIONS:
Degenerate discs treated with 5 mg/mL of simvastatin in a hydrogel carrier demonstrated radiographic and histologic features resembling normal noninjured IVDs. In addition, the gene expression of aggrecan and collagen type II (important constituents of the IVD extracellular matrix) was upregulated in treated discs. Injection of simvastatin into degenerate IVDs may result in retardation of disc degeneration and represents a promising investigational therapy for conservative treatment of DDD.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Regeneration
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Simvastatin
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Intervertebral Disc Degeneration
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Intervertebral Disc
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Spine J
Journal subject:
ORTOPEDIA
Year:
2014
Document type:
Article
Affiliation country:
United States
Publication country:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
/
USA