The interaction of monocytes with rheumatoid synovial cells is a key step in LIGHT-mediated inflammatory bone destruction
The interaction of monocytes with rheumatoid synovial cells is a key step in LIGHT-mediated inflammatory bone destruction
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DOI：
10.1111/j.1365-2567.2008.02965.x
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发表时间：
2009-09-01
期刊：
影响因子：
6.4
通讯作者：
Suzuki, Ryuji
中科院分区：
文献类型：
--
作者：
Ishida, Satoru;Yamane, Shoji;Suzuki, Ryuji
破骨细胞的形成和随之而来的关节破坏是类风湿关节炎(RA)的特征。在此，我们发现肿瘤坏死因子超家族成员LIGH可以诱导CD14(+)单核细胞向抗酒石酸酸性磷酸酶(TRAP)阳性的多核细胞分化，但不能诱导新分离的CD14(+)单核细胞分化为抗酒石酸酸性磷酸酶(TRAP)阳性的多核细胞。核因子-kappa B受体激活剂配体(RANKL)促进了这种光诱导的TRAP阳性单核细胞的产生。MNC具有破骨细胞的表型和功能特征，表达组织蛋白酶K、肌动蛋白环形成和骨吸收能力等破骨细胞标志物。此外，在RANKL诱导的CD14+单核细胞中，MNC同时表达基质金属蛋白酶9(MMP9)和MMP12，而MNCs不表达MMP12。免疫组织化学分析显示，类风湿关节炎患者关节侵蚀区存在产生基质金属蛋白酶-12的单核细胞，而骨性关节炎患者病变关节无表达。这些发现提示LIGH可能参与RA炎症性骨破坏的过程，破骨细胞前体细胞可能通过与滑膜细胞样的护士样细胞相互作用而具有光介导的破骨细胞生成能力。
P>Formation of osteoclasts and consequent joint destruction are hallmarks of rheumatoid arthritis (RA). Here we show that LIGHT, a member of the tumour necrosis factor (TNF) superfamily, induced the differentiation into tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs) of CD14(+) monocytes cocultured with nurse-like cells isolated from RA synovium, but not of freshly isolated CD14(+) monocytes. Receptor activator of nuclear factor-kappa B ligand (RANKL) enhanced this LIGHT-induced generation of TRAP-positive MNCs. The MNCs showed the phenotypical and functional characteristics of osteoclasts; they showed the expression of osteoclast markers such as cathepsin K, actin-ring formation, and the ability to resorb bone. Moreover, the MNCs expressed both matrix metalloproteinase 9 (MMP-9) and MMP-12, but the latter was not expressed in osteoclasts induced from CD14(+) monocytes by RANKL. Immunohistochemical analysis showed that the MMP-12-producing MNCs were present in the erosive areas of joints in RA, but not in the affected joints of osteoarthritic patients. These findings suggested that LIGHT might be involved in the progression of inflammatory bone destruction in RA, and that osteoclast progenitors might become competent for LIGHT-mediated osteoclastogenesis via interactions with synoviocyte-like nurse-like cells.