Kaji H, Kanatani M, Sugimoto T, Chihara K
Division of Endocrinology/Metabolism, Neurology and Hematology/Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Horm Metab Res. 2005 Oct;37(10):589-92. doi: 10.1055/s-2005-870538.
Statins stimulate bone formation partly by inducing osteoblast differentiation, although there is controversy about the effects of statins on bone mineral density and fracture risk. Several studies have revealed that statins suppress bone resorption. However, the mechanism by which statins inhibit bone resorption is still unclear. The present study was performed to clarify the effects of statins on osteoclast formation as well as the levels of osteoprotegerin (OPG) and receptor activator of NFkappaB ligand (RANKL) mRNA in mouse bone-cell cultures by semiquantitative RT-PCR. 10(-8) M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] significantly stimulated osteoclast formation and 10(-6) M statins (mevastatin and simvastatin) significantly antagonized osteoclast formation stimulated by 1,25(OH)2D3 in mouse bone-cell cultures, including both osteoblasts and osteoclasts. 10(-6) M mevastatin and simvastatin increased the level of OPG mRNA in mouse bone-cell cultures. On the other hand, 10(-6) M mevastatin and simvastatin inhibited the level of RANKL mRNA in these cultures. In conclusion, the present study demonstrates that statins inhibit osteoclast formation in mouse bone-cell cultures. Moreover, statins also increased and decreased the levels of OPG and RANKL mRNA expression in these cultures, respectively. The modulation of OPG/RANKL may be involved in the inhibition of osteoclast formation by statins.
他汀类药物部分通过诱导成骨细胞分化来刺激骨形成，尽管关于他汀类药物对骨矿物质密度和骨折风险的影响存在争议。多项研究表明他汀类药物可抑制骨吸收。然而，他汀类药物抑制骨吸收的机制仍不清楚。本研究旨在通过半定量逆转录聚合酶链反应（RT-PCR）阐明他汀类药物对小鼠骨细胞培养物中破骨细胞形成以及骨保护素（OPG）和核因子κB受体活化因子配体（RANKL）mRNA水平的影响。10(-8)M 1,25-二羟基维生素D3[1,25(OH)2D3]显著刺激破骨细胞形成，而10(-6)M他汀类药物（美伐他汀和辛伐他汀）在小鼠骨细胞培养物（包括成骨细胞和破骨细胞）中显著拮抗1,25(OH)2D3刺激的破骨细胞形成。10(-6)M美伐他汀和辛伐他汀增加了小鼠骨细胞培养物中OPG mRNA的水平。另一方面，10(-6)M美伐他汀和辛伐他汀抑制了这些培养物中RANKL mRNA的水平。总之，本研究表明他汀类药物在小鼠骨细胞培养物中抑制破骨细胞形成。此外，他汀类药物还分别增加和降低了这些培养物中OPG和RANKL mRNA表达水平。OPG/RANKL的调节可能参与了他汀类药物对破骨细胞形成的抑制作用。
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