BCMA expression in rheumatoid arthritis fibroblast-like synovial cells

纤维母细胞样滑膜细胞（FLS）是类风湿关节炎（RA）发病机制中的主要效应细胞之一。我们最近报道了增殖诱导配体（四月份）的多种刺激作用，以及它对RA滑膜中FLS的特异性作用（RA-FLS）。RA血清中可溶性APRIL含量明显高于正常血清。在4月的三种受体中，RA-FLS仅表达B细胞成熟抗原（BCMA），而骨性关节炎滑膜中的FLS （OA-FLS）不表达任何受体。APRIL刺激RA-FLS产生白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α、IL-1β和APRIL本身。APRIL还增强了RA-FLS中核因子κ b配体受体激活因子（RANKL）的表达。BCMA表达的调控机制尚未被充分描述。票据。1是一种转录共激活因子，已被证明可以调节PU的表达。1.在本研究中，我们证明了RA-FLS表达转录因子PU。1和转录共激活子OBF。1、PU的表达水平。RA-FLS中1、OBF-1与BCMA相关。这些结果表明，APRIL是RA发病的主要调节因子之一。BCMA转录的表观遗传调控可能有助于这种情况的潜在机制。因此，BCMA和APRIL都可以被认为是潜在的治疗靶点，以改善RA患者患关节的损伤。

Fibroblast-like synoviocytes(FLS) are among the principal effector cells in the pathogenesis of rheumatoid arthritis(RA). We recently reported the variety of stimulating effects of a proliferation-inducing ligand(APRIL), and its specific effect on the FLS in the affected RA synovium(RA-FLS). A significantly higher level of soluble APRIL was detected in RA serum than in normal serum. Among the three receptors of APRIL tested, RA-FLS expressed only B cell maturation antigen(BCMA), whereas the FLS in the affected osteoarthritis synovium(OA-FLS) expressed none of the receptors. APRIL stimulated RA-FLS but not OA-FLS to produce interleukin(IL)-6, tumor necrosis factor(TNF)-α, IL-1β and APRIL itself. APRIL also enhanced the receptor activator of nuclear factor kappaB ligand(RANKL) expression in RA-FLS.The regulatory mechanisms of BCMA expression have not been fully described. OBF. 1 is a transcriptional co-activator, and has been shown to regulate the expression of PU. 1.In this study, we demonstrated that RA-FLS expressed transcription factor PU. 1 and transcriptional co-activator OBF. 1, and the expression levels of PU. 1 and OBF-1 were correlated with those of BCMA in RA-FLS.These results provide evidence that APRIL is one of the main regulators in the pathogenesis of RA. Epigenetic regulation of BCMA transcription might contribute to the underlying mechanisms of this condition. Thus, both BCMA and APRIL could be considered as potential therapeutic targets in ameliorating damage to the affected joints of patients with RA.