Intradiscal injection of simvastatin retards progression of intervertebral disc degeneration induced by stab injury.
BACKGROUND
Earlier work indicates that the cholesterol-lowering drug, simvastatin, is anabolic to chondrogenic expression of rat intervertebral disc (IVD) cells, which suggests a potential role for simvastatin in IVD regeneration. In this study, we expand on our earlier work to test the effectiveness of simvastatin on disc degeneration utilizing a rat tail disc degeneration model.


METHODS
30 rats that underwent 21 G needle-puncture at rat tail discs were injected with simvastatin-loaded poly(ethylene glycol)-poly(lactic acid-co-glycolic acid)-poly(ethylene glycol) (PEG-PLGA-PEG) gel (5 mg/ml) or vehicle control at 4 weeks after needle injury. All animals were sacrificed 2 weeks after simvastatin injection. Bone morphogenetic protein-2 (BMP-2), aggrecan, collagen type II, and collagen type I messenger ribonucleic acid (mRNA) expression in the rat nucleus pulposus (NP) were measured by real-time polymerase chain reaction (PCR). In vivo magnetic resonance imaging (MRI) was performed to monitor changes in disc degeneration. Rat discs were also assessed by histology using hematoxylin and eosin (H&E) and safranin O staining. In addition, the NP weight, glycosaminoglycan (sGAG) and DNA content were also measured.


RESULTS
A single dose of simvastatin loaded in thermo-sensitive PEG-PLGA-PEG gel injected into the NP had the trend to increase aggrecan expression and sGAG content, and significantly increased mRNA levels of BMP-2, collagen type II, and the differentiation index (the ratio of collagen type II to collagen type I). The decreased NP weight, T2 intensity, as well as MRI index in the rat tail discs induced by needle puncture were significantly reversed after 2 weeks of simvastatin treatment. In addition, simvastatin treatment also improved histological changes induced by needle puncture.


CONCLUSIONS
A single injection of simvastatin loaded in PEG-PLGA-PEG gel into rat tail discs had the potential to retard or regenerate the degenerative disc.
Zhang
Huina
H
Spine Research Laboratory, Department of Neurosurgery, University of Michigan Medical School, 1500 E, Medical Center Drive, Ann Arbor, Michigan 48109, USA. hnzhang@umich.edu
Wang
Lin
L
Park
Jun Beom
JB
Park
Paul
P
Yang
Victor C
VC
Hollister
Scott J
SJ
La Marca
Frank
F
Lin
Chia-Ying
CY
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis / Q000187:drug effects*; D004337:Drug Carriers / Q000008:administration & dosage; D005782:Gels; D015870:Gene Expression / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007403:Intervertebral Disc / Q000187:drug effects* / Q000293:injuries; D055959:Intervertebral Disc Degeneration / Q000188:drug therapy*; D019344:Lactic Acid / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011100:Polyglycolic Acid / Q000008:administration & dosage; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019821:Simvastatin / Q000008:administration & dosage*
D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D005782:Gels; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D019821:Simvastatin