外源性骨强化蛋白对强直性脊柱炎小鼠的疗效研究 .pdfVIP

外源性骨强化蛋白对强直性脊柱炎小鼠的疗效研究

刘亚;张晓军

【摘要】目的：评估外源性骨强化蛋白(sclerostin,SOST)治疗强直性脊柱炎的疗

效。方法BALB/cIL-4小鼠每隔2周皮下注射2mg人蛋白多糖,8周后诱导脊柱

炎(PGISp)模型,PGISp小鼠体内SOST表达下调。随后将PGISp小鼠根据治疗方

案,分为SOST组与阳性对照组。SOST组注射2.5μg重组SOST(recombinant

SOST,rSOST),持续8周。阳性对照组注射同剂量外源性Wnt通路抑制因子

Dickkopf1(DKK-1),同样持续8周。使用双能X线骨密度仪(DEXA)检测2组小鼠

组织学和骨骼变化,评估外周关节及中轴骨疾病的发展状况。结果SOST组外周或

轴向疾病发展,骨质密度或疾病严重程度均无改善。rSOST注射8h达到峰值,注射

24h后血浆SOST质量浓度水平较高,导致循环系统SOST血清水平累积。免疫组

化法检查骨细胞水平,阳性对照组中未受累关节内骨细胞水平显著低于受累关节内

骨细胞水平；SOST组小鼠不同关节之间的骨细胞水平无差异。组间未受累关节进

行比较,阳性对照组优于SOST组。结论rSOST未能降低关节内的骨细胞水平,但

其具有生物活性。今后需要改变剂量,提高骨靶向能力,从而影响骨生成；目前外源

性骨强化蛋白疗效不及DKK-1。%ObjectiveToevaluatethecurativeeffectof

exogenousbonestrengtheningprotein(sclerostin,SOST)forthetreatment

ofankylosingspondylitis.MethodsTheproteoglycan(2mg)-induced

spondylitis(PGISp)mousemodelinwhichwepreviouslydemonstrated

downregulatedSOSTexpression,wasusedforthisstudy.Micewere

injectedwith2.5μgrSOST/dayforaperiodof8weeksfollowinginduction

ofdisease.SamedoseDickkopf1(DKK-1)wasinjectedincontrolgroup,also

8weeks.Axialskele-tondiseasedevelopmentwasassessedbyhistology

andskeletalchangesexaminedusingDEXA.ResultsSOSTtreatmenthadno

effectonperipheraloraxialdiseasedevelopment,bonedensityordisease

severity.InjectedrSOSTwasstableover8handresiduallevelswereevident

24hafterinjection,resultinginacumulativeincreaseinSOSTserumlevels

overthetreatmenttimecourse.Immunohistochemicalexaminationof

SOSTlevelswithinthejointsincontrolgroupshowedasignificant

decreaseinthepercentageofpositiveosteocytesintheunaffectedjoints

comparedtotheaffectedjoints,whilenodifferencewasobservedinSOST

treatedmice.ThissuggeststhatrSOSTtreatmentincreasesthenumberof

SOST-positiveosteocytesinunaffectedjointsbutnotaffected

joints,despiteofhavingnoimpactonthenumberofjointsaffectedby