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


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


METHODS
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.
Department of Orthopedics, National Taiwan University College of Medicine and National Taiwan University Hospital, No. 7, Jhong-Shan S Rd, Taipei, 10002, Taiwan; Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1 Ren-Ai Rd, Sec. 1, Taipei, 10051, Taiwan.
Ming-Hsiao
MH
Hu
Department of Dental Technology, College of Oral Medicine, Taipei Medical University, No. 250, Wu-Hsing St, Taipei, 11031, Taiwan.
Kai-Chiang
KC
Yang
Department of Orthopedics, Far Eastern Memorial Hospital, No. 21, Nanya S Rd, Sec. 2, New Taipei City, 22060, Taiwan.
Yeong-Jang
YJ
Chen
Department of Orthopedics, National Taiwan University College of Medicine and National Taiwan University Hospital, No. 7, Jhong-Shan S Rd, Taipei, 10002, Taiwan.
Yuan-Hui
YH
Sun
Department of Orthopedics, National Taiwan University College of Medicine and National Taiwan University Hospital, No. 7, Jhong-Shan S Rd, Taipei, 10002, Taiwan. Electronic address: shuhuayang@ntu.edu.tw.
Shu-Hua
SH
Yang
D053674:Aggrecans / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D007403:Intervertebral Disc / Q000187:drug effects* / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000473:pathology / Q000517:prevention & control*; D008148:Lovastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D055758:SOX9 Transcription Factor / Q000378:metabolism
D053674:Aggrecans; D055396:Bone Morphogenetic Protein 2; D024042:Collagen Type I; D024043:Collagen Type II; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D055758:SOX9 Transcription Factor; D008148:Lovastatin
Bone morphogenetic protein-2; Degeneration; Discography; Intervertebral disc; Lovastatin; Nucleus pulposus; SOX9