机械加载通过促进髌下脂肪垫干细胞迁移及软骨分化治疗骨关节炎  

Mechanical loading treats osteoarthritis by promoting the migration and chondrogenic differentiation of infrapatellar fat pad stem cells

作　　者：王筱郁 李杰 李心乐[1,2] 刘大全 张平 WANG Xiao-yu;LI Jie;LI Xin-le;LIU Da-quan;ZHANG Ping(Department of Anatomy and Histology,School of Basic Medical Sciences,Tianjin Medical University,Tianjin 300070,China;Key Laboratory of Hormones and Development(Ministry of Health),Tianjin Key Laboratory of Metabolic Diseases,Tianjin 300134,China;Tianjin Key Laboratory of Spine and Spinal Cord,Tianjin 300052,China)

机构地区：[1]天津医科大学基础医学院人体解剖与组织胚胎学系,天津300070 [2]卫生部激素与发育重点实验室,天津市代谢性疾病重点实验室,天津300134 [3]天津市脊柱脊髓重点实验室,天津300052

出　　处：《天津医科大学学报》2022年第5期508-512,554,共6页Journal of Tianjin Medical University

基　　金：天津市教委科研计划项目(2019KJ169)。

摘　　要：目的:探究机械加载对骨关节炎小鼠髌下脂肪垫干细胞(IFP-SCs)的动员作用。方法:54只雌性C57BL/6小鼠通过随机数字表法分为对照组(Sham组,n=18)、骨关节炎组(OA组,n=18)、骨关节炎机械加载组(OAL组,n=18)。采用DMM手术建立OA模型,OAL组进行2周的机械加载治疗(条件为1 N,5 Hz,6 min/d)。HE和番红O染色评估小鼠OA模型的软骨损伤程度。免疫荧光、细胞迁移实验、Western印迹等方法检测干细胞的迁移和软骨形成能力。结果:机械加载降低了OA小鼠的国际骨关节炎研究学会(OARSI)评分(t=4.025,P<0.01)。与OA组相比,OAL组IFP-SCS的迁移能力增加(t=-5.142,P<0.001),同时软骨中基质细胞衍生因子(SDF-1)和IFP-SCs中C-X-C趋化因子受体4(CXCR4)的表达增加(t=-4.403,P<0.01)。此外,机械加载使软骨分化中重要的转录因子SRY相关高迁移率族盒蛋白9(SOX9)上调,促进了IFP-SCs软骨分化(t=-11.170,P<0.01)。结论:机械加载通过促进IFP-SCs迁移和软骨分化,促进骨关节炎小鼠软骨修复。Objective:To explore the effect of mechanical loading on the mobilization of infrapatellar fat pad stem cells(IFP-SCs)in osteoarthritis mice.Methods:Fifty-four female C57BL/6 mice were divided into three groups by random number table method:the sham control group(Sham,n=18),the osteoarthritis group(OA,n=18),and the osteoarthritis with mechanical loading group(OAL group,n=18).The OA model was established by DMM surgery.The OAL group received loading treatment for 2 weeks(the conditions are 1 N,5 Hz,6 min/d).The degree of cartilage damage in a mouse model of osteoarthritis was evaluated with HE and Safranin O staining.Immunofluorescence,cell migration assay,and Western blotting analysis were used to evaluate the migration and chondrogenic formation ability of stem cells.Results:Mechanical loading reduced the OARSI(Osteoarthritis Research Society International)score of OA mice(t=4.025,P<0.01).Compared with the OA group,the migration of IFP-SCs was enhanced(t=-5.142,P<0.001),and the expression of stromal cell derived factor-1(SDF-1)in cartilage and C-X-C motif chemokine receptor 4(CXCR4)in infrapatellar fat pad stem cells(IFP-SCs)were increased(t=-4.403,P<0.01).In addition,mechanical loading promoted IFP-SCs chondrogenic differentiation via up-regulation of SRY-related high mobility group-box 9(SOX9)which was an important transcription factor in chondrogenic differentiation(t=-11.170,P<0.01).Conclusion:Mechanical loading facilitates cartilage repair in osteoarthritis mice by promoting the migration and chondrogenic differentiation of infrapatellar fat pad stem cells.

关 键 词：机械加载 骨关节炎 髌下脂肪垫干细胞 迁移 软骨分化 

分 类 号：R684.3[医药卫生—骨科学]