Schelbergen R F, van Dalen S, ter Huurne M, Roth J, Vogl T, Noël D, Jorgensen C, van den Berg W B, van de Loo F A, Blom A B, van Lent P L E M
Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
Osteoarthritis Cartilage. 2014 Aug;22(8):1158-66. doi: 10.1016/j.joca.2014.05.022. Epub 2014 Jun 10.
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.
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.
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-1beta (IL-1β) and KC was down-regulated in the synovium. IL-1β 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.
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.
滑膜炎在相当一部分骨关节炎（OA）患者中很明显，且与病理生理学的发展相关。最近我们发现脂肪来源干细胞（ASC）可抑制胶原酶诱导的实验性骨关节炎（CIOA）中的关节破坏。在本研究中，我们探讨了滑膜炎和警戒素S100A8/A9在实验性骨关节炎中ASC免疫调节能力的作用。
以滑膜炎为特征的CIOA和手术诱导的内侧半月板失稳（DMM）性骨关节炎均接受ASC局部治疗。在组织学切片上测量滑膜激活、软骨损伤和骨赘大小。使用Luminex或酶联免疫吸附测定法（S100A8/A9）测定滑膜冲洗液和血清中的细胞因子，用逆转录（RT）-qPCR测定mRNA水平。
在DMM诱导后的不同时间点（第7天或第14天）局部给予ASC对OA病理无影响。在CIOA的第7天，ASC注射后6小时，滑膜中促炎介质S100A8/A9、白细胞介素-1β（IL-1β）和KC的mRNA表达就已下调。IL-1β蛋白水平虽低，但经ASC治疗的CIOA中其水平下调。S100A8/A9蛋白水平在6小时和48小时时非常高，经ASC治疗后降低。仅当沉积时滑膜炎症严重（以血清S100A8/A9水平高为反映）时，ASC治疗在CIOA中才具有保护作用。最后，成功治疗导致血清S100A8/A9水平显著降低。
我们的研究表明，滑膜激活迅速驱动关节内注射的ASC在实验性骨关节炎中的抗炎和保护作用，这通过S100A8/A9水平降低得以体现。
