Department of Periodontology, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
J Periodontal Res. 2011 Aug;46(4):483-90. doi: 10.1111/j.1600-0765.2011.01364.x. Epub 2011 Apr 4.
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.
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.
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.
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.
三羟基-3-甲基戊二酰基辅酶 A（HMG-CoA）还原酶竞争性抑制剂，即“他汀类药物”，被广泛用于降低胆固醇，从而降低心脏病发作的风险。最近的数据表明，他汀类药物通过对三种分子的作用影响代谢性骨活性：RANKL；RANK；以及核因子-κB 受体活化因子配体（RANKL）的可溶性诱饵受体骨保护素（OPG）。本研究旨在评估他汀类药物对静止和白细胞介素-1β（IL-1β）激活的人牙龈成纤维细胞（HGF）中 OPG 和 RANKL 产生的影响，并确定其对这些细胞产生的影响。
将成纤维细胞在无血清培养基中用阿托伐他汀或辛伐他汀预孵育 24h，然后用 IL-1β 孵育 6d。通过特定的 ELISA 测量培养上清液中 OPG 或 RANKL 的浓度。使用方差分析和 Scheffe 的 F 程序进行事后比较分析数据。
IL-1β（1×10(-8) m）刺激 OPG 的产生在第 1、3 和 6 天显著增加。IL-1β 刺激后 RANKL 产生呈增加趋势。两种他汀类药物在多个浓度下均显著增加了 RANKL/OPG 的固有比率。只有阿托伐他汀在最高浓度（5×10(-6) m）时显著增加了 IL-1β 刺激的 RANKL/OPG 比率。
IL-1β 显著增加了 HGF 中 OPG 的产生。他汀类药物在对静止和 IL-1β 激活的 HGF 中 OPG 和 RANKL 产生的影响方面差异极小。两种他汀类药物均增加了 RANKL/OPG 的固有比率，但通常不增加 IL-1β 刺激的比率。因此，在非炎症条件下，他汀类药物可能会影响 HGF 中 RANKL 和 OPG 的产生，从而有利于骨分解代谢。
