Lories Rik J U
Laboratory for Skeletal Development and Joint Disorders, Division of Rheumatology, University Hospitals Leuven, Katholieke Universiteit Leuven, Belgium.
Curr Opin Rheumatol. 2006 Jul;18(4):342-6. doi: 10.1097/01.bor.0000231900.81677.c5.
The aim of this article is to review new insights into spondyloarthritis obtained in animal models during the last year.
HLA-B27 misfolding has been demonstrated in HLA-B27/human beta2-microglobulin transgenic rats. HLA-B27 misfolding is associated with a typical unfolded protein stress response and with an interferon-response signature. Prebiotic treatment of these rats reduced colitis and arthritis. Proteoglycan-induced spondylitis is distinct from proteoglycan-induced arthritis. Specific susceptibility loci for proteoglycan-induced spondylitis have been demonstrated. Bone morphogenetic proteins are important in new cartilage and bone formation in ankylosing enthesitis. Psoriasis and psoriatic arthritis-like disease develops in conditional double JunB/c-Jun knockout mice.
Insights into the molecular signaling pathways driving HLA-B27 associated spondylitis, autoimmune spondylitis, ankylosing enthesitis and psoriasis, resulting from animal models, identify new and specific therapeutic targets in spondyloarthritis.
本文旨在回顾过去一年在动物模型中获得的关于脊柱关节炎的新见解。
在HLA - B27/人β2 - 微球蛋白转基因大鼠中已证实HLA - B27错误折叠。HLA - B27错误折叠与典型的未折叠蛋白应激反应及干扰素反应特征相关。对这些大鼠进行益生元治疗可减轻结肠炎和关节炎。蛋白聚糖诱导的脊柱炎与蛋白聚糖诱导的关节炎不同。已证实了蛋白聚糖诱导的脊柱炎的特定易感基因座。骨形态发生蛋白在强直性附着点炎的新软骨和骨形成中起重要作用。在条件性双JunB/c - Jun基因敲除小鼠中会发生银屑病和银屑病关节炎样疾病。
动物模型对驱动HLA - B27相关脊柱炎、自身免疫性脊柱炎、强直性附着点炎和银屑病的分子信号通路的见解,确定了脊柱关节炎新的特异性治疗靶点。