Objective: To study the effect of pioglitazone, a synthetic peroxisome proliferator-activated receptor γ (PPARγ) agonist, on the RANKL-mediated osteoclastogenesis of osteoclast precursor cells, and to explore the function and mechanism of PPARγ in the osteoclast differentiation.
Methods: Pioglitazone treatment of RAW264.7 murine macrophages were compared with those of simply cultured control and RANKL-mediated control. Accordingly, the RANKL-mediated cells were cultured with 30 ng/ml RANKL, then induced into significant multinuclear osteoclast formation. And pioglitazone treated cells were exposed to 10 µmol/L pioglitazone during the process of osteoclast differentiation under RANKL. The number of mature osteoclasts was calculated and the mRNA levels of RANK analyzed by real-time quantitative PCR.
Results: Pioglitazone significantly inhibited osteoclastogenesis of osteoclast precursor cells, the number of mature osteoclasts of pioglitazone treated group was (176 ± 58)/cm(2) and significantly less than the mature cells of RANKL induced group which number was (322 ± 74)/cm(2) (P < 0.01); and pioglitazone also significantly inhibited the mRNA expression of RANK, a typical differentiated factor of osteoclast, the number of the mRNA expression of RANK of pioglitazone treated group was 2.16 ± 0.74 and significantly less than the number of RANKL induced group (4.94 ± 0.39, P < 0.01).
Conclusion: PPARγ agonist inhibited the differentiation of RAW264.7 towards osteoclast. It might be due to the suppression of RANK gene expression in the process of osteoclast differentiation.