Lefèvre Stephanie, Knedla Anette, Tennie Christoph, Kampmann Andreas, Wunrau Christina, Dinser Robert, Korb Adelheid, Schnäker Eva-Maria, Tarner Ingo H, Robbins Paul D, Evans Christopher H, Stürz Henning, Steinmeyer Jürgen, Gay Steffen, Schölmerich Jürgen, Pap Thomas, Müller-Ladner Ulf, Neumann Elena
Department of Internal Medicine and Rheumatology, Justus-Liebig-University Giessen, Kerckhoff-Clinic, Bad Nauheim, Germany.
Nat Med. 2009 Dec;15(12):1414-20. doi: 10.1038/nm.2050. Epub 2009 Nov 8.
Active rheumatoid arthritis originates from few joints but subsequently affects the majority of joints. Thus far, the pathways of the progression of the disease are largely unknown. As rheumatoid arthritis synovial fibroblasts (RASFs) which can be found in RA synovium are key players in joint destruction and are able to migrate in vitro, we evaluated the potential of RASFs to spread the disease in vivo. To simulate the primary joint of origin, we implanted healthy human cartilage together with RASFs subcutaneously into severe combined immunodeficient (SCID) mice. At the contralateral flank, we implanted healthy cartilage without cells. RASFs showed an active movement to the naive cartilage via the vasculature independent of the site of application of RASFs into the SCID mouse, leading to a marked destruction of the target cartilage. These findings support the hypothesis that the characteristic clinical phenomenon of destructive arthritis spreading between joints is mediated, at least in part, by the transmigration of activated RASFs.
活动性类风湿性关节炎起源于少数关节，但随后会影响大多数关节。迄今为止，该疾病的进展途径在很大程度上尚不清楚。由于在类风湿性关节炎滑膜中发现的类风湿性关节炎滑膜成纤维细胞（RASFs）是关节破坏的关键因素，并且能够在体外迁移，我们评估了RASFs在体内传播疾病的可能性。为了模拟最初发病的关节，我们将健康的人软骨与RASFs一起皮下植入严重联合免疫缺陷（SCID）小鼠体内。在对侧胁腹，我们植入了无细胞的健康软骨。RASFs通过脉管系统向未受影响的软骨进行活跃迁移，且与RASFs在SCID小鼠体内的植入部位无关，导致靶软骨明显破坏。这些发现支持了以下假说：关节间破坏性关节炎的典型临床现象至少部分是由活化的RASFs迁移介导的。
