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Statins regulate interleukin-1β-induced RANKL and osteoprotegerin production by human gingival fibroblasts
S H Stein1, I N Dean, S Y Rawal
1Department of Periodontology, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA. sstein@uthsc.edu
Insights
Statins may influence bone metabolism by altering osteoprotegerin (OPG) and RANKL production in human gingival fibroblasts (HGFs). While interleukin-1β increased OPG, statins primarily affected the RANKL/OPG ratio under non-inflammatory conditions.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Statins (HMG-CoA reductase inhibitors) are widely used for cholesterol management.
- Emerging evidence suggests statins impact bone metabolism via RANKL, RANK, and OPG pathways.
- Understanding statin effects on OPG and RANKL in specific cell types is crucial.
Purpose of the Study:
- To investigate OPG and RANKL production in human gingival fibroblasts (HGFs).
- To assess the influence of interleukin-1β (IL-1β) on OPG and RANKL secretion.
- To determine the effects of statins on OPG and RANKL production in HGFs.
Main Methods:
- Human gingival fibroblasts (HGFs) were treated with atorvastatin or simvastatin.
- Cells were stimulated with IL-1β in serum-free conditions.
- OPG and RANKL concentrations in culture supernatants were quantified using ELISA.
Main Results:
- IL-1β significantly elevated OPG production by HGFs.
- A trend towards increased RANKL production was observed with IL-1β stimulation.
- Statins increased the constitutive RANKL/OPG ratio, with minimal impact on IL-1β-stimulated ratios.
Conclusions:
- IL-1β enhances OPG production in HGFs.
- Statins appear to influence RANKL/OPG balance, potentially favoring bone resorption under non-inflammatory conditions.
- Further research is needed to elucidate the precise role of statins in bone metabolism.
Background And Objective:
Three-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase competitive inhibitors, or 'statins', are widely used for lowering cholesterol and thereby reducing the risk of a heart attack. Recent data suggest that statins influence metabolic bone activity by their actions on three molecules: RANKL; RANK; and osteoprotegerin (OPG), the soluble decoy receptor for RANKL. The purpose of this study was to evaluate OPG and RANKL production in resting and interleukin-1β (IL-1β)-activated human gingival fibroblasts (HGFs), and to determine the effect of statins on their production.
Material And Methods:
Fibroblasts were pre-incubated with atorvastatin or simvastatin for 24h in serum-free medium, and then incubated with IL-1β for 6d. The concentration of OPG or RANKL in culture supernatants was measured by specific ELISA. Data were analyzed using analysis of variance and Scheffe's F procedure for post hoc comparison.
Results:
IL-1β (1×10(-8) m) stimulated a significant increase in the production of OPG on days 1, 3 and 6. There was a trend towards an increase in RANKL production as a result of stimulation with IL-1β. Both statins, at multiple concentrations, significantly increased the constitutive RANKL/OPG ratio. Only atorvastatin at the highest concentration (5×10(-6) m) significantly increased the IL-1β-stimulated RANKL/OPG ratio.
Conclusion:
IL-1β significantly increased OPG production by HGFs. The statins differed minimally in their effects on OPG and RANKL production by resting and IL-1β-activated HGFs. Both statins increased constitutive RANKL/OPG ratios, but generally not IL-1β-stimulated ratios. Thus, statins may influence the production of RANKL and OPG by HGFs to favor bone catabolism, under noninflammatory conditions.
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