吡格列酮对单核细胞RAW264.7向破骨细胞分化过程中核因子κB受体活化因子的影响  

Effect of pioglitazone on receptor activator of nuclear factor-kappa B expression in osteoclast from RAW264.7 cells

作　　者：姜敏[2] 吕珊[1] 吴琳[1] 刘娟[1] 程鹏[1] 丁国宪[1] 

机构地区：[1]南京医科大学第一附属医院老年医学科,210029 [2]南京医科大学鼓楼临床医学院老年医学科

出　　处：《中华医学杂志》2010年第32期2282-2285,共4页National Medical Journal of China

基　　金：基金项目：国家自然科学基金青年基金（30900505）

摘　　要：目的 探讨过氧化物酶体增殖物激活受体γ（PPARγ）在破骨细胞分化过程中的作用及机制.方法 将小鼠单核细胞RAW264.7分为正常对照组、核因子κB受体活化子配体（RANKL）诱导组（使用30μg/L的RANKL诱导RAW264.7向破骨细胞分化）和吡格列酮刺激组（在使用30 μg/L的RANKL诱导破骨细胞分化的同时给予10μmol/L的吡格列酮刺激,持续至分化全程）,待破骨细胞分化成熟以后进行破骨细胞染色、计数,并利用实时定量PCR检测单核细胞向破骨细胞分化过程中核因子κB受体活化子（RANK）的mRNA表达量.结果 吡格列酮抑制单核细胞RAW264.7向破骨细胞分化,吡格列酮组的破骨细胞数目（176±58）个/cm2明显低于RANKL诱导组（322±74）个/cm2,差异有统计学意义（P＜0.01） 吡格列酮抑制单核细胞RAW264.7分化过程中RANK的mRNA表达量,对照组（1.13±0.26） 吡格列酮组（2.16±0.74）明显低于RANKL诱导组（4.94±0.39）,差异有统计学意义（P＜0.01）.结论 吡格列酮抑制了单核细胞RAW264.7向破骨细胞的分化,这可能与PPARγ激动剂下调了RANK的表达,进一步抑制破骨细胞分化有关.Objective To study the effect of pioglitazone, a synthetic peroxisome proliferator-activated receptorγ （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 ）/cm2 and significantly less than the mature cells of RANKL induced group which number was （322 ±74）/cm2 （P〈0.01） and pioglitazone also significantly inhibited the mRNA expression of RANK, a typical differentiated fator 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 differentitation of RAW264.7 towards osteoclast. It might be due to the suppression of RANK gene expression in the process of osteoclast differentiation.

关 键 词：过氧化物酶体增殖物激活受体 破骨细胞 吡格列酮 

分 类 号：R965[医药卫生—药理学]