罗格列酮对破骨细胞生成的影响

Effect of rosiglitazone on osteoclastogenesis： an in vitro study

目的探讨罗格列酮对破骨细胞生成的影响。方法取C57BIM6小鼠骨髓内单个核细胞，用细胞核因子kappaB受体活化因子配基（RANKL）及巨噬细胞集落刺激因子（M—CSF）诱导其向破骨细胞分化，在诱导开始时即分成3组：空白对照组（G1），0．5μmoL／L罗格列酮组（G2），2．0μmol／L罗格列酮组（G3），诱导结束后进行抗酒石酸酸性磷酸酶（TRAP）染色、检测TRAP活性以及实时PCR检测相关基因的表达。应用单因素方差分析进行统计学分析。结果破骨细胞生成的数目在G2组[（54±5）个]、G3组[（72±5）个]均高于G1组[（32±5）个]，差异有统计学意义（F=82．43，P〈0．05），TRAP活性也高于对照组（G1：2．32±0．14，G2：2．83±0．08，G3：3．35±0．10，F=108．12，P〈0．05）；过氧化物酶增殖物激活受体-γ（PPAR-γ）、组织蛋白酶K、c-fos与c-jun基因表达也高于对照组，且随着罗格列酮的浓度升高，相关基因的表达也增高（F值分别为33．50、37．46、53．73、39．77，均P〈0．05）。结论罗格列酮可能通过促进细胞增殖而促进破骨细胞生成，这司能是罗格列酮导致骨丢失的重要原因之一。

Objective To investigate the effect of rosiglitazone on osteoclastogenesis. Methods Monocytes from bone marrow were isolated from the C57BL/6 mice and induced to differentiate into osteoclasts. Meanwhile, osteoclasts were incubated in the control group （ G1 ） , 0. 5 μmol/L rosiglitazone （ G2 ） and 2.0 μmoL/L rosiglitazone （ G3 ）. Four days after cell culture, tartrate resistant acid phosphatase （TRAP） staining, osteoclast cell counting, real-time PCR analysis and quantitative measurement of TRAP activity were respectively done. Results For the number of osteoclastogenesis, the G2 and G3 group were significantly increased compared to the G1 group （ G1 ： 32 ± 5, G2 ： 54 ± 5, G3 ： 72 ± 5, F = 82. 43, P 〈 0.05） ; for TRAP activity assay, the G2 and G3 group were also increased compared to G1 group（G1：2.32±0.14,G2：2.83±0.08,G3：3.35±0.10,F=108.12,P〈0.05）. The gene expression in osteoelast, such as peroxisome proliferator activated receptor gamma, cathepsin k, c-fos and c-jun, were increased in rosiglitazone groups compared to the control group（ F value was 33.50, 37.46, 53.73, 39. 77, respectively, all P 〈 0. 05 ）. Conclusion Rosiglitazone may increases osteoclastogenesis by cell proliferation.