Examining the effects of HMG-CoA reductase inhibitors on anabolic and catabolic signaling pathway proteins associated with degenerative disc disease

I. Yilmaz, N. Karaarslan

Unit of Pharmacovigilance, and Rational Use of Drugs, Republic of Turkey, Ministry of Health, Dr. Ismail Fehmi Cumalioglu Hospital, Tekirdag, Turkey. dryilmazi@yahoo.com

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• Pharmacology

OBJECTIVE: Recent evidence suggests that statins, among lipid-lowering drugs, can be used to lower serum cholesterol levels for reducing the risk of cardiovascular disease in individuals with high cholesterol, as well as reducing DNA damage and having anti-ageing and pleiotropic effects. Additionally, nuclear factor kappa B (NF-κB) is reported to be suppressed in statin-administered nucleus pulposus (NP) cells for the prevention of interleukin (IL) -1 beta (IL-1β)-induced apoptosis and extracellular matrix (ECM) degradation. The purpose of this study is the examine whether it is possible for pharmacological synthetic statin agents added into primary cell cultures obtained from human intervertebral disc tissue (IVD) to stop and eliminate tissue degeneration through the anabolic/catabolic signaling pathways associated with inflammation.

MATERIALS AND METHODS: Pitavastatin and rosuvastatin were added to monolayer grown human primary annulus fibrosus (AF)/NP cells. Cytotoxicity and proliferation analyses were carried out. AF/NP cells and ECM structure were also examined microscopically. In addition, changes in transcription factors and protein expressions of proinflammatory cytokines, which play important roles in anabolic and catabolic pathways associated with inflammation, were analyzed.

RESULTS: Decreased proliferation and cell necrosis were observed at the end of 72 hours in the samples, in which statins were added, compared to the samples in the control group to which no pharmacological agent was administered. In addition to this, changes were observed in the expressions of proteins. All results were statistically significant (p<0.05).

CONCLUSIONS: To better understand the regenerative effects of these two pharmacological agents on degenerated AF/NP cells, there is an urgent need for prospective studies in which different signaling pathways and receptors on these pathways are investigated, apart from IL-1β; NF-κB signaling pathway and SOX9.

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