Institute of Pathology, University Hospital, Jena, Germany.
Institute of Clinical Chemistry and Laboratory Medicine, University Hospital, Am Klinikum 1, D-07743, Jena, Germany.
Arthritis Res Ther. 2018 Nov 22;20(1):261. doi: 10.1186/s13075-018-1720-y.
Fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) are autonomously activated to maintain inflammation and joint destruction in co-transplantation models. To elucidate inducing mechanisms involved in this altered behavior, the arthritogenic potential of FLSs from murine antigen-induced arthritis (AIA) were investigated in a transfer model.
FLSs were isolated, expanded in vitro, and transferred into knee joint cavities of severe combined immunodeficient (SCID) mice. Their arthritogenic capacity was assessed by monitoring joint swelling and evaluation of histological parameters 70 to 100 days after transfer.
FLSs from AIA mice were able to transfer arthritis into recipient SCID mice. FLS transfer induced a chronic arthritis with recruitment of inflammatory cells and marked cartilage destruction. Long-lasting inflammation was not required for imprinting of arthritogenicity in FLSs since cells isolated from acute arthritic joints were fully competent to transfer arthritis. We also observed arthritogenic potential in FLSs isolated from contralateral non-arthritic joints in our monoarticular arthritis model.
We show that the transformation of FLSs into arthritogenic cells occurs early in arthritis development. This challenges current hypotheses on the role of these cells in arthritis pathogenesis and opens up the way for further mechanistic studies.
类风湿关节炎（RA）患者的成纤维样滑膜细胞（FLS）在共移植模型中自主激活，以维持炎症和关节破坏。为了阐明这种改变行为涉及的诱导机制，在转移模型中研究了来自鼠抗原诱导关节炎（AIA）的 FLS 的致关节炎潜力。
分离、体外扩增 FLS，并转移到严重联合免疫缺陷（SCID）小鼠的膝关节腔中。在转移后 70 至 100 天，通过监测关节肿胀和评估组织学参数来评估其致关节炎能力。
AIA 小鼠的 FLS 能够将关节炎转移到受体 SCID 小鼠中。FLS 转移诱导慢性关节炎，伴有炎症细胞募集和明显的软骨破坏。在 FLS 中印记致关节炎性不需要持久的炎症，因为从急性关节炎关节分离的细胞完全有能力转移关节炎。在我们的单关节炎模型中，我们还观察到来自对侧非关节炎关节的 FLS 具有致关节炎潜力。
我们表明，FLS 向致关节炎细胞的转化发生在关节炎发展的早期。这挑战了这些细胞在关节炎发病机制中的作用的现有假说，并为进一步的机制研究开辟了道路。
