基质细胞衍生因子-1 alpha与Dickkopf-1相互作用参与多发性骨髓瘤骨病发生  

Interaction between Stromal Cell-Derived Factor 1 Alpha and Dickkopf-1 Involves in Occurence of Myeloma Bone Disease

作　　者：昝芸艳 刘扬[2] 笪熠[3] 庄俊玲[1] ZAN Yun-Yan;LIU Yang;DA Yi;ZHUANG Jun-Ling(Department of Hematology,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China;Department of Hematology,Peking University People’s Hospital,Beijing 100044,China;Department of Endocrinology,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医学院,北京协和医院血液内科,北京100730 [2]北京大学附属人民医院血液内科,北京100044 [3]中国医学科学院北京协和医学院,北京协和医院内分泌科,北京100730

出　　处：《中国实验血液学杂志》2020年第5期1592-1597,共6页Journal of Experimental Hematology

基　　金：北京市自然科学基金(7192175)。

摘　　要：目的:评价促进破骨细胞活性的基质衍生因子-1α(SDF-1α)和抑制成骨细胞的dickkopf-1(DKK-1)之间是否相互作用并促进多发性骨髓瘤(MM)骨病的发生。方法:收集2011年6月至2014年5月北京协和医院51例新诊断MM患者、30例健康对照者和35例非霍奇金淋巴瘤患者的血清标本,采用ELISA方法测定血清SDF-1α和DKK-1水平。SDF-1α刺激人MM细胞株RPMI 8226及MM患者原代骨髓瘤细胞,应用RT-PCR检测DKK-1 mRNA水平。体外培养MM患者原代骨髓基质细胞(BMSC),加入DKK-1或/和Wnt-3a后检测SDF-1αmRNA转录水平变化。结果:51例新诊断MM患者血清SDF-1α水平为(3231.0±1269.5)pg/ml,显著高于健康对照组[(2817.5±419.6)pg/ml(P=0.036)]。MM患者血清DKK-1水平为(3057.4±1874.7)pg/ml,也显著高于健康对照组[(1867.7±1148.4)pg/ml](P=0.01)。MM患者SDF-1α和DKK-1水平呈正相关(r=0.301,P=0.032),健康对照组(r=0.15,P=0.428)和非霍奇金淋巴瘤组(r=0.227,P=0.095)未显示二者存在相关性。人MM细胞株RPMI8226经SDF-1α作用8和36 h后,DKK-1 mRNA的转录水平分别上升至1.92倍及4.19倍(P=0.365,P=0.099)。9例MM患者中有5例基线DKK-1 mRNA为高转录水平,经SDF-1α处理后出现转录上调(P=0.043)。Wnt-3a使原代BMSC SDF-1αmRNA表达下降至基线的29%(P=0.028),加入DKK-1可逆转这一下调作用。结论:MM患者血清SDF-1α与DKK-1水平高于正常,且具有正相关性,二者相互促进,加剧MM骨病发生。Objective:To explore the role of interaction between osteoclast stimulator stromal derived factor 1 alpha(SDF-1α)and osteoblast inhibitor dickkopf-1(DKK-1)in the development of multiple myeloma(MM)bone disease.Methods:The serum samples of 51 patients with newly diagnosed MM,30 age-matched healthy controls,and 35 nonHodgkin lymphoma patients from June 2011 to May 2014 in Peking Union Medical College Hospital were collected.The serum SDF-1αand DKK-1 were detected by ELISA.Primary myeloma cells and human MM cell line RPMI 8226 were treated with SDF-1α,then DKK-1 mRNA expression was detected by real time PCR.Primary bone marrow stromal cells(BMSCs)were treated with Wnt-3 a and/or DKK-1,and the transc-ription level of SDF-1αmRNA was assayed.Results:Serum SDF-1αin MM patients was significantly higher than that in control group(3231.0±1269.5 pg/ml vs2817.5±419.6 pg/ml)(P=0.036),so was serum DKK-1(3057.4±1874.7 pg/ml vs 1867.7±1148.4 pg/ml)(P=0.01).There was a positive correlation between serum SDF-1αand DKK-1 in MM patients(r=0.301,P=0.032),but there was no correlation between control group(r=0.15,P=0.428)and non-Hodgkin lymphoma patients(r=0.227,P=0.095).After treated with SDF-1α(20 ng/ml)for 8 and 36 h,the DKK-1 mRNA transcription level in RPMI 8226 increased by 1.92 and 4.19-folds respectively(P=0.365,P=0.099).Moreover,the high transcription level of DKK-1 mRNA was observed in 5 out of 9 MM patients.The detection showed that after treatment with SDF-1α,the transcription level was up-regulated(P=0.043),the Wnt-3 a(200 ng/ml)could decrease the expression of SDF-1αmRNA in primary BMSC to 29%of baseline(P=0.028),the adding DKK-1 could reverse the down-regulation effect.Conclusion:The serum SDF-1αand DKK-1 level in MM patients is high than normal leve,moreover shows the positive correlation between them.The SDF-1αand DKK-1 can interreact,therefore accerate the formation of MM bone disease.

关 键 词：多发性骨髓瘤骨病 基质衍生因子-1α DICKKOPF-1 

分 类 号：R733.3[医药卫生—肿瘤]