Osteoclasts are responsible for bone destruction in rheumatoid arthritis (RA), and adipose‐derived mesenchymal stromal cells (ADSCs) can inhibit experimental collagen‐induced arthritis model. This study aims to determine whether ADSCs also suppresses osteoclastogenesis and bone erosion in collagen‐induced arthritis (CIA). Osteoclasts were induced from bone marrow‐derived CD11b⁺ cells with receptor activator of nuclear factor‐κ B ligand (RANKL) and macrophage colony‐stimulating factor (M‐CSF) stimulation and assessed with tartrate‐resistant acid phosphatase (TRAP) staining. For human cells, osteoclasts were produced from human CD14⁺ cells. ADSCs were generated and added to cultures with different ratios with CD11b⁺ cells. Transwell and antibody blockade experiments were performed to define the mechanism of action. NF‐κB and RANKL expression were determined by Western blotting and RT‐qPCR. About 2 × 10⁶ ADSCs or fibroblast cells were adoptively transferred to DBA1/J mice on day 14 after immunization with type II collagen/complete Freund's adjuvant (CII/CFA) while the onset and severity of the CIA were monitored. Adipose‐derived mesenchymal stromal cells but not fibroblast cells completely suppressed osteoclastogenesis in vitro for human and mice. ADSCs injected after immunization and before of onset of CIA significantly suppressed disease development. Treatment with ADSCs dramatically decreased the levels of NF‐κB p65/p50 in osteoclasts in vitro and P65/50 and RANKL expression by synovial tissues in vivo. We have demonstrated that ADSCs can inhibit RANKL‐induced osteoclasts genesis via CD39 signals. Our findings also suggest that ADSCs can inhibit osteoclasts genesis without the involvement of regulatory T cells. ADSCs might represent a promising strategy for stem cell‐based therapies for RA. Thus, manipulation of ADSCs may have therapeutic effects on RA and other bone erosion–related diseases.

中文翻译：

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脂肪来源的间充质基质细胞抑制胶原诱导的关节炎中的破骨细胞生成和骨侵蚀。

破骨细胞负责类风湿关节炎 (RA) 的骨破坏，而脂肪来源的间充质基质细胞 (ADSC) 可以抑制实验性胶原诱导的关节炎模型。本研究旨在确定 ADSCs 是否也抑制胶原诱导关节炎 (CIA) 中的破骨细胞生成和骨侵蚀。破骨细胞是由骨髓来源的 CD11b ⁺细胞用核因子-κ B 配体 (RANKL) 受体激活剂和巨噬细胞集落刺激因子 (M-CSF) 刺激诱导的，并用耐酒石酸酸性磷酸酶 (TRAP) 染色进行评估。对于人类细胞，破骨细胞是由人类 CD14 ⁺细胞产生的。生成 ADSC 并将其添加到具有不同比例的 CD11b ^{+培养物中}细胞。进行 Transwell 和抗体阻断实验以确定作用机制。通过蛋白质印迹和 RT-qPCR 测定 NF-κB 和 RANKL 的表达。约 2 × 10 ⁶在用 II 型胶原/完全弗氏佐剂 (CII/CFA) 免疫后的第 14 天，将 ADSC 或成纤维细胞过继转移至 DBA1/J 小鼠，同时监测 CIA 的发作和严重程度。脂肪来源的间充质基质细胞而非成纤维细胞在体外完全抑制人和小鼠的破骨细胞生成。在免疫后和 CIA 发病前注射的 ADSC 显着抑制了疾病的发展。ADSCs 治疗显着降低了体外破骨细胞中 NF-κB p65/p50 的水平以及体内滑膜组织中 P65/50 和 RANKL 的表达。我们已经证明 ADSC 可以通过 CD39 信号抑制 RANKL 诱导的破骨细胞生成。我们的研究结果还表明，ADSCs 可以在不涉及调节性 T 细胞的情况下抑制破骨细胞的发生。ADSCs 可能代表一种有前途的基于干细胞的 RA 治疗策略。因此，ADSCs 的操作可能对 RA 和其他骨侵蚀相关疾病具有治疗作用。