Statins regulate interleukin-1β-induced RANKL and osteoprotegerin production by human gingival fibroblasts
| Autor: | David A. Tipton, I. N. Dean, Swati Y Rawal, Sidney H. Stein |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
musculoskeletal diseases
medicine.medical_specialty biology business.industry Catabolism Cholesterol Atorvastatin chemistry.chemical_compound Endocrinology medicine.anatomical_structure chemistry Osteoprotegerin Simvastatin RANKL Internal medicine biology.protein Periodontics Medicine business Receptor Fibroblast medicine.drug |
| Zdroj: | Journal of Periodontal Research. 46:483-490 |
| ISSN: | 0022-3484 |
| DOI: | 10.1111/j.1600-0765.2011.01364.x |
| Popis: | Stein SH, Dean IN, Rawal SY, Tipton DA. Statins regulate interleukin-1β - induced RANKL and osteoprotegerin production by human gingival fibroblasts. J Periodont Res 2011; 46: 483–490. © 2011 John Wiley & Sons A/S 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 24 h in serum-free medium, and then incubated with IL-1β for 6 d. 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. |
| Databáze: | OpenAIRE |
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