Treatment efficacy of adipose-derived stem cells in experimental osteoarthritis is driven by high synovial activation and reflected by S100A8/A9 serum levels

被引：97

作者：

Schelbergen, R. F. ^{[1
]}

van Dalen, S. ^{[1
]}

ter Huurne, M. ^{[1
]}

Roth, J. ^{[2
]}

Vogl, T. ^{[2
]}

Noel, D. ^{[3
]}

Jorgensen, C. ^{[3
]}

van den Berg, W. B. ^{[1
]}

van de Loo, F. A. ^{[1
]}

Blom, A. B. ^{[1
]}

van Lent, P. L. E. M. ^{[1
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands

[2] Univ Munster, Inst Immunol, Munster, Germany

[3] Hop St Eloi, Inserm U844, Montpellier, France

来源：

OSTEOARTHRITIS AND CARTILAGE | 2014年 / 22卷 / 08期

关键词：

Adipose stem cells; S100; Synovitis; Animal models; Experimental OA; OSTEOPHYTE FORMATION; RHEUMATOID-ARTHRITIS; KNEE OSTEOARTHRITIS; LINING MACROPHAGES; CRUCIAL ROLE; INFLAMMATION; CARTILAGE; DISEASE; EXPRESSION; INJECTION;

D O I：

10.1016/j.joca.2014.05.022

中图分类号：

R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学（修复外科学）];

学科分类号：

100224 [整形外科学];

摘要：

Objective: Synovitis is evident in a substantial subpopulation of patients with osteoarthritis (OA) and is associated with development of pathophysiology. Recently we have shown that adipose-derived stem cells (ASC) inhibit joint destruction in collagenase-induced experimental OA (CIOA). In the current study we explored the role of synovitis and alarmins S100A8/A9 in the immunomodulatory capacity of ASCs in experimental OA. Method: CIOA, characterized by synovitis, and surgical DMM (destabilization of medial meniscus) OA were treated locally with ASCs. Synovial activation, cartilage damage and osteophyte size were measured on histological sections. Cytokines in synovial washouts and serum were determined using Luminex or enzyme-linked immunosorbent assay (S100A8/A9), mRNA levels with reverse-transcriptase (RT)-qPCR. Results: Local administration of ASCs at various time-points (days 7 or 14) after DMM induction had no effect on OA pathology. At day 7 of CIOA, already 6 h after ASC injection mRNA expression of pro-inflammatory mediators S100A8/A9, interleukin-1 beta (IL-1 beta) and KC was down-regulated in the synovium. IL-1 beta protein, although low, was down-regulated by ASC-treatment of CIOA. S100A8/A9 protein levels were very high at 6 and 48 h and were decreased by ASC-treatment. The protective action of ASC treatment in CIOA was only found when high synovial inflammation was present at the time of deposition which was reflected by high serum S100A8/A9 levels. Finally, successful treatment resulted in significantly lower levels of serum S100A8/A9. Conclusion: Our study indicates that synovial activation rapidly drives anti-inflammatory and protective effects of intra-articularly deposited ASCs in experimental OA which is reflected by decreased S100A8/A9 levels. (C) 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

引用

页码：1158 / 1166

页数：9

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