Statins Modulate the Levels of Osteoprotegerin/Receptor Activator of NFκB Ligand mRNA in Mouse Bone-cell Cultures

Abstract

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 NFκB 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.

Key words

Statin - Osteoclast formation - Osteoprotegerin - Osteoclast - RANKL

References

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