Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, 280 South Chongqing Road, Shanghai 200025, China.
Guanghua Rheumatology Hospital, 540 Xinhua Road, Shanghai 200052, China.
Biomed Res Int. 2018 Feb 19;2018:4901591. doi: 10.1155/2018/4901591. eCollection 2018.
Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by bone loss. Degree of inflammation has been identified as an important initiator of skeletal damage in RA. Iguratimod (T-614) is an anti-inflammatory agent which has been reported to show the inhibitory effect of bone destruction in RA. However, the role of T-614 in osteoblast differentiation is still not clear. In this study, we intended to find the effect of T-614 on the osteogenesis process. We detected osteogenesis markers and transcription factors associated with osteoblastic lineage and bone formation in the culture of mesenchymal stem cells which differentiate osteoblast. The contents and activity of alkaline phosphatase, levels of collagen type I and bone gla protein, and calcium nodule formation were increased significantly after T-614 treated. Meanwhile, the mRNAs expressions of and were also found to be increased significantly by real-time PCR. The changes of levels of phosphorylation of p38 and NF-B were also detected by Western blot. The results showed that T-614 promotes osteoblastic differentiation by increasing the expression of and and increasing the activation of P38. T-614 could advance the ectopic expression of NF-B to suppress inflammation, which indirectly inhibits the damage of the osteoblasts.
类风湿关节炎（RA）是一种以骨丢失为特征的自身免疫性炎症性疾病。炎症程度已被确定为 RA 中骨骼破坏的重要启动因素。来氟米特（T-614）是一种具有抗炎作用的药物，据报道其具有抑制 RA 中骨破坏的作用。然而，T-614 在成骨细胞分化中的作用尚不清楚。在这项研究中，我们旨在研究 T-614 对成骨过程的影响。我们检测了间充质干细胞分化为成骨细胞的培养物中与成骨细胞谱系和骨形成相关的成骨标志物和转录因子。用 T-614 处理后，碱性磷酸酶的含量和活性、I 型胶原和骨钙素水平以及钙结节形成均显著增加。同时，实时 PCR 也发现 和 的 mRNAs 表达显著增加。通过 Western blot 还检测到 p38 和 NF-B 磷酸化水平的变化。结果表明，T-614 通过增加 和 的表达以及增加 P38 的激活来促进成骨细胞分化。T-614 可以促进 NF-B 的异位表达以抑制炎症，从而间接抑制成骨细胞的损伤。
