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Anti-osteoarthritis effect of a combination treatment with human adipose tissue-derived mesenchymal stem cells and thrombospondin 2 in rabbits

查看全文 作　　者：Kyungha [1]Shin;Yeseul [1]Cha;Young-Hwan [1]Ban;Da Woom [1]Seo;Ehn-Kyoung [1]Choi;Dongsun [2]Park;Sung Keun [3]Kang;Jeong Chan [3]Ra;Yun-Bae [1]Kim 高影响力作者 机构地区：[1]College of Veterinary Medicine,Chungbuk National University,Cheongju 28644,Chungbuk,South Korea;[2]Department of Biology Education,Korea National University of Education,Cheongju 28173,Chungbuk,South Korea;[3]Biostar Stem Cell Research Institute,R-BIO Co.,Ltd.,Seoul 07238,South Korea高影响力机构 出　　处：《World Journal of Stem Cells》索引2019年第11卷第12期,共15页高影响力期刊 基　　金：Supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT to Y.B.K.,No.2017R1A2A2A05069417 摘　　要：BACKGROUND Osteoarthritis(OA),a chronic age-related disease characterized by the slowly progressive destruction of articular cartilage,is one of the leading causes of disability.As a new strategy for treatment of OA,mesenchymal stem cells(MSCs)have the potential for articular cartilage regeneration.Meanwhile,thrombospondin 2(TSP2)promotes the chondrogenic differentiation of MSCs.AIM To investigate whether TSP2 induces chondrogenic differentiation of human adipose-derived MSCs(hADMSCs)and potentiates the therapeutic effects of hADMSCs in OA rabbits.METHODS We investigated the chondrogenic potential of TSP2 in hADMSCs by analyzing the expression of chondrogenic markers as well as NOTCH signaling genes in normal and TSP2 small interfering RNA(siRNA)-treated stem cells.Anterior cruciate ligament transection surgery was performed in male New Zealand white rabbits,and 8 wk later,hADMSCs(1.7×10^6 or 1.7×10^7 cells)were injected into the injured knees alone or in combination with intra-articular injection of TSP2(100 ng/knee)at 2-d intervals.OA progression was monitored by gross,radiological,and histological examinations.RESULTS In hADMSC culture,treatment with TSP2 increased the expression of chondrogenic markers(SOX9 and collagen Ⅱ)as well as NOTCH signaling genes(JAGGED1 and NOTCH3),which were inhibited by TSP2 siRNA treatment.In vivo,OA rabbits treated with hADMSCs or TSP2 alone exhibited lower degree of cartilage degeneration,osteophyte formation,and extracellular matrix loss 8 wk after cell transplantation.Notably,such cartilage damage was further alleviated by the combination of hADMSCs and TSP2.In addition,synovial inflammatory cytokines,especially tumor-necrosis factor-α,markedly decreased following the combination treatment.CONCLUSION The results indicate that TSP2 enhances chondrogenic differentiation of hADMSCs via JAGGED1/NOTCH3 signaling,and that combination therapy with hADMSCs and TSP2 exerts synergistic effects in the cartilage regeneration of OA joints. 关 键 词：Osteoarthritis Anterior CRUCIATE LIGAMENT TRANSECTION HUMAN ADIPOSE tissuederived mesenchymal stem cell THROMBOSPONDIN 2 Notch signaling Cartilage regeneration
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