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Intradiscal injection of simvastatin results in radiologic, histologic, and genetic evidence of disc regeneration in a rat model of degenerative disc disease.

Publication ,  Journal Article
Than, KD; Rahman, SU; Wang, L; Khan, A; Kyere, KA; Than, TT; Miyata, Y; Park, Y-S; La Marca, F; Kim, HM; Zhang, H; Park, P; Lin, C-Y
Published in: Spine J
June 1, 2014

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.

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Published In

Spine J

DOI

EISSN

1878-1632

Publication Date

June 1, 2014

Volume

14

Issue

6

Start / End Page

1017 / 1028

Location

United States

Related Subject Headings

  • Up-Regulation
  • Simvastatin
  • Regeneration
  • Rats, Sprague-Dawley
  • Rats
  • Orthopedics
  • Male
  • Magnetic Resonance Imaging
  • Intervertebral Disc Degeneration
  • Intervertebral Disc
 

Citation

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Than, K. D., Rahman, S. U., Wang, L., Khan, A., Kyere, K. A., Than, T. T., … Lin, C.-Y. (2014). 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), 1017–1028. https://doi.org/10.1016/j.spinee.2013.11.034
Than, Khoi D., Shayan U. Rahman, Lin Wang, Adam Khan, Kwaku A. Kyere, Tracey T. Than, Yoshinari Miyata, et al. “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, no. 6 (June 1, 2014): 1017–28. https://doi.org/10.1016/j.spinee.2013.11.034.
Than, Khoi D., et al. “Intradiscal injection of simvastatin results in radiologic, histologic, and genetic evidence of disc regeneration in a rat model of degenerative disc disease.Spine J, vol. 14, no. 6, June 2014, pp. 1017–28. Pubmed, doi:10.1016/j.spinee.2013.11.034.
Than KD, Rahman SU, Wang L, Khan A, Kyere KA, Than TT, Miyata Y, Park Y-S, La Marca F, Kim HM, Zhang H, Park P, Lin C-Y. Intradiscal injection of simvastatin results in radiologic, histologic, and genetic evidence of disc regeneration in a rat model of degenerative disc disease. Spine J. 2014 Jun 1;14(6):1017–1028.
Journal cover image

Published In

Spine J

DOI

EISSN

1878-1632

Publication Date

June 1, 2014

Volume

14

Issue

6

Start / End Page

1017 / 1028

Location

United States

Related Subject Headings

  • Up-Regulation
  • Simvastatin
  • Regeneration
  • Rats, Sprague-Dawley
  • Rats
  • Orthopedics
  • Male
  • Magnetic Resonance Imaging
  • Intervertebral Disc Degeneration
  • Intervertebral Disc