Courbon Guillaume, Cleret Damien, Linossier Marie-Thérèse, Vico Laurence, Marotte Hubert
SAINBIOSE, INSERM U1059, LBTO, Saint-Etienne, France.
University of Lyon, Saint-Etienne, France.
J Cell Physiol. 2017 Jun;232(6):1318-1325. doi: 10.1002/jcp.25601. Epub 2017 Jan 5.
Synovitis is usually observed before loss of articular function in rheumatoid arthritis (RA). In addition to the synovium and according to the "Inside-Outside" theory, bone compartment is also involved in RA pathogenesis. Then, we investigated time dependent articular bone loss and prediction of early bone loss to late arthritis severity on the rat adjuvant-induced arthritis (AIA) model. Lewis female rats were longitudinally monitored from arthritis induction (day 0), with early (day 10) and late (day 17) steps. Trabecular and cortical microarchitecture parameters of four ankle bones were assessed by microcomputed tomography. Gene expression was determined at sacrifice. Arthritis occurred at day 10 in AIA rats. At this time, bone erosions were detected on four ankle bones, with cortical porosity increase (+67%) and trabecular alterations including bone volume fraction (BV/TV: -13%), and trabecular thickness decrease. Navicular bone assessment was the most reproducible and sensitive. Furthermore, strong correlations were observed between bone alterations at day 10 and arthritis severity or bone loss at day 17, including predictability of day 10 BV/TV to day 17 articular index (R = 0.76). Finally, gene expression at day 17 confirmed massive osteoclast activation and interestingly provided insights on strong activation of bone formation inhibitor markers at the joint level. In rat AIA, bone loss was already observed at synovitis onset and was predicted late arthritis severity. Our results reinforced the key role of subchondral bone in arthritis pathogenesis, in favour to the "Inside-Outside" theory. Mechanisms of bone loss in rat AIA involved resorption activation and formation inhibition changes. J. Cell. Physiol. 232: 1318-1325, 2017. © 2016 Wiley Periodicals, Inc.
滑膜炎通常在类风湿关节炎（RA）关节功能丧失之前就已出现。除了滑膜之外，根据“由内而外”理论，骨组织也参与了RA的发病机制。随后，我们在大鼠佐剂性关节炎（AIA）模型上研究了关节骨丢失的时间依赖性以及早期骨丢失对晚期关节炎严重程度的预测作用。从关节炎诱导期（第0天）开始对雌性Lewis大鼠进行纵向监测，分为早期（第10天）和晚期（第17天）两个阶段。通过微型计算机断层扫描评估四个踝关节的小梁和皮质微结构参数。在处死时测定基因表达。AIA大鼠在第10天出现关节炎。此时，在四个踝关节上检测到骨侵蚀，皮质孔隙率增加（+67%），小梁结构改变包括骨体积分数（BV/TV：-13%）以及小梁厚度减小。舟骨评估的重复性和敏感性最高。此外，在第10天的骨改变与第17天的关节炎严重程度或骨丢失之间观察到强相关性，包括第10天的BV/TV对第17天关节指数的预测性（R = 0.76）。最后，第17天的基因表达证实破骨细胞大量激活，有趣的是，还揭示了关节水平骨形成抑制标志物的强烈激活情况。在大鼠AIA中，滑膜炎发作时就已出现骨丢失，并且可以预测晚期关节炎的严重程度。我们的结果强化了软骨下骨在关节炎发病机制中的关键作用，支持“由内而外”理论。大鼠AIA中骨丢失的机制涉及吸收激活和形成抑制的变化。《细胞生理学杂志》2017年第232卷：1318 - 1325页。© 2016威利期刊公司
