Abstract | STUDY DESIGN: In vitro experiment to study the effect of simvastatin on rat intervertebral disc (IVD) cells. OBJECTIVE: To evaluate the time-course effect of simvastatin on the gene expression of bone morphogenetic protein-2 (BMP-2), aggrecan, and collagen type II in rat IVD cells cultured in alginate bead. Role of BMP-2 on the simvastatin-induced chondrogenesis of IVD cells was also investigated. SUMMARY OF BACKGROUND DATA:
Growth factors including BMP-2 have been found to improve anabolism of IVD cells and have shown promise for the treatment of disc degeneration. Statins is known to increase BMP-2 expression in vitro and stimulate bone formation in vivo. However, it is still unknown whether statins can also increase BMP-2 expression and in turn, stimulate matrix synthesis by IVD cells. METHODS: Rat IVD cells (harvested from nucleus pulpusos and inner annular fibrosus) cultured in alginate beads were exposed to different doses of simvastatin. DMMB, and real-time polymerase chain reaction were used to quantify proteoglycan and gene expression of BMP-2, aggrecan and collagen type II, respectively. Noggin or mevalonate was used to investigate the mechanism of the effect of simvastatin on rat IVD cells. RESULTS: CONCLUSION:
Simvastatin drives a mechanism for promoting chondrogenesis of IVD cells partially mediated by upregulated BMP-2 through the inhibition of mevalonate pathway.
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Authors | Huina Zhang, Chia-Ying Lin |
Journal | Spine
(Spine (Phila Pa 1976))
Vol. 33
Issue 16
Pg. E525-31
(Jul 15 2008)
ISSN: 1528-1159 [Electronic] United States |
PMID | 18628692
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Bone Morphogenetic Protein 2
- Simvastatin
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Topics |
- Animals
- Bone Morphogenetic Protein 2
(biosynthesis, genetics)
- Cells, Cultured
- Chondrocytes
(cytology, drug effects, metabolism)
- Chondrogenesis
(drug effects, physiology)
- Intervertebral Disc
(cytology, drug effects, metabolism)
- Phenotype
- Rats
- Rats, Sprague-Dawley
- Signal Transduction
(drug effects, physiology)
- Simvastatin
(pharmacology)
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