Plasma cells promote osteoclastogenesis and periarticular bone loss in autoimmune arthritis
Plasma cells promote osteoclastogenesis and periarticular bone loss in autoimmune arthritis
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浆细胞促进自身免疫性关节炎破骨细胞生成和关节周围骨丢失
DOI：
10.1172/jci143060
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发表时间：
2021-03-15
影响因子：
15.9
通讯作者：
Takayanagi, Hiroshi
中科院分区：
文献类型：
--
作者：
Komatsu, Noriko;Win, Stephanie;Takayanagi, Hiroshi
在类风湿性关节炎（RA）中，骨钙素骨吸收导致结构性关节损伤以及关节周围和全身骨丢失。关节周围骨丢失是RA的最早指标之一，通常通过很大程度上未知的机制先于临床症状的发作。滑膜成纤维细胞表达的NF-κ B配体受体激活因子（RANKL）诱导的破骨细胞过度生成导致关节侵蚀，而淋巴细胞表达的RANKL在各种类型的骨损伤中的作用尚未阐明。在关节炎小鼠的骨髓中，我们发现表达RANKL的浆细胞数量增加，其显示出体外诱导破骨细胞生成的能力。在自身免疫性关节炎中，B系细胞中RANKL的基因消除导致关节周围骨丢失的改善，但不导致关节侵蚀或全身性骨丢失。我们还显示了决定性的证据，滑膜成纤维细胞RANKL的关键贡献的关节侵蚀胶原诱导的关节炎的关节炎的DBA/1 J背景。这项研究强调了浆细胞RANKL在关节炎关节周围骨丢失中的重要性，并为自身免疫诱导的骨病变的早期表现提供了机制上的见解。
In rheumatoid arthritis (RA), osteoclastic bone resorption causes structural joint damage as well as periarticular and systemic bone loss. Periarticular bone loss is one of the earliest indices of RA, often preceding the onset of clinical symptoms via largely unknown mechanisms. Excessive osteoclastogenesis induced by receptor activator of NF-kappa B ligand (RANKL) expressed by synovial fibroblasts causes joint erosion, whereas the role of RANKL expressed by lymphocytes in various types of bone damage has yet to be elucidated. In the bone marrow of arthritic mice, we found an increase in the number of RANKL-expressing plasma cells, which displayed an ability to induce osteoclastogenesis in vitro. Genetic ablation of RANKL in B-lineage cells resulted in amelioration of periarticular bone loss, but not of articular erosion or systemic bone loss, in autoimmune arthritis. We also show conclusive evidence for the critical contribution of synovial fibroblast RANKL to joint erosion in collagen-induced arthritis on the arthritogenic DBA/1J background. This study highlights the importance of plasma-cell RANKL in periarticular bone loss in arthritis and provides mechanistic insight into the early manifestation of bone lesion induced by autoimmunity.