Department of Physiology and Immunology, University of Zagreb School of Medicine, Zagreb, Croatia.
J Rheumatol. 2010 Feb;37(2):246-56. doi: 10.3899/jrheum.090167. Epub 2009 Dec 15.
To assess whether different forms of arthritis and disease activity could be distinguished by peripheral blood expression profiles of bone-regulatory factors including tumor necrosis factor (TNF)-superfamily [TNF-related apoptosis-inducing ligand (TRAIL), the Fas ligand (FasL), and the ligand for herpesvirus entry mediator (LIGHT)] and bone morphogenetic protein (BMP)-family members (BMP-2, BMP-4, BMP-6) as well as osteoblast differentiation gene Runx2.
Blood cells from healthy controls (n = 25) and patients at different disease stages with rheumatoid arthritis (RA; n = 49), osteoarthritis (OA; n = 17), or spondyloarthritis, including ankylosing spondylitis (AS; n = 27) or psoriatic arthritis (PsA; n = 23), were processed for quantitative polymerase chain reaction. Gene expression was assessed in comparison with control samples, correlated with clinical data of different forms of arthritis, and analyzed for discriminative efficacy between groups by receiver-operation characteristic (ROC) curves. Results were confirmed on diagnostic RA (n = 5) and AS (n = 8) samples.
BMP-4, BMP-6, and Runx2 expressions were significantly decreased in patients with RA and OA versus controls. Patients with RA also had decreased FasL and LIGHT expression, while patients with AS had increased Runx2 expression. Negative correlation with disease activity was found for BMP-4, FasL, and Runx2 in RA and for Runx2 in PsA, while positive correlation was found for BMP-4 in PsA. Gene expression was higher in the therapy-resistant form of AS (for BMP-4, LIGHT, and Runx2) and in methotrexate-treated patients in RA (for BMP-2 and LIGHT). ROC curve analysis confirmed discrimination between groups, particularly decreased LIGHT and Runx2 for RA and increased Runx2 for AS.
Our study identified BMP and Runx2 as possible biomarkers of bone metabolism in several forms of arthritis, while lower FasL and LIGHT were associated with RA. Correlation between gene expression and disease activity may be clinically useful in assessing therapeutic effectiveness and disease monitoring.
评估外周血中骨调节因子（包括肿瘤坏死因子（TNF）超家族[肿瘤坏死因子相关凋亡诱导配体（TRAIL）、Fas 配体（FasL）和疱疹病毒进入介质配体（LIGHT）]和骨形态发生蛋白（BMP）家族成员（BMP-2、BMP-4、BMP-6）以及成骨细胞分化基因 Runx2 的表达谱是否可以区分不同形式的关节炎和疾病活动。
从健康对照者（n=25）和处于不同疾病阶段的类风湿关节炎（RA；n=49）、骨关节炎（OA；n=17）或脊柱关节炎患者（包括强直性脊柱炎（AS；n=27）或银屑病关节炎（PsA；n=23）的血液细胞中提取。与对照样本进行比较，评估基因表达，并与不同形式关节炎的临床数据相关联，并通过接收者操作特征（ROC）曲线分析组间的判别效能。结果在诊断为 RA（n=5）和 AS（n=8）的样本中得到了验证。
与对照组相比，RA 和 OA 患者的 BMP-4、BMP-6 和 Runx2 表达明显降低。RA 患者的 FasL 和 LIGHT 表达也降低，而 AS 患者的 Runx2 表达增加。在 RA 中，BMP-4、FasL 和 Runx2 与疾病活动呈负相关，在 PsA 中与 Runx2 呈正相关。在 AS 的治疗抵抗形式（BMP-4、LIGHT 和 Runx2）和 RA 中接受甲氨蝶呤治疗的患者（BMP-2 和 LIGHT）中，基因表达更高。ROC 曲线分析证实了组间的区分，特别是 RA 中的 LIGHT 和 Runx2 降低以及 AS 中的 Runx2 升高。
我们的研究确定了 BMP 和 Runx2 作为几种形式关节炎骨代谢的可能生物标志物，而 FasL 和 LIGHT 较低则与 RA 相关。基因表达与疾病活动之间的相关性可能在评估治疗效果和疾病监测方面具有临床意义。
