Lories Rik J U, Derese Inge, Luyten Frank P
Laboratory for Skeletal Development and Joint Disorders, Department of Rheumatology, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.
J Clin Invest. 2005 Jun;115(6):1571-9. doi: 10.1172/JCI23738. Epub 2005 May 12.
Joint ankylosis is a major cause of disability in the human spondyloarthropathies. Here we report that this process partially recapitulates embryonic endochondral bone formation in a spontaneous model of arthritis in DBA/1 mice. Bone morphogenetic protein (BMP) signaling appears to be a key molecular pathway involved in this pathological cascade. Systemic gene transfer of noggin, a BMP antagonist, is effective both as a preventive and a therapeutic strategy in the mouse model, mechanistically interfering with enthesial progenitor cell proliferation in early stages of the disease process. Immunohistochemical staining for phosphorylated smad1/5 in enthesial biopsies of patients with spondyloarthropathy reveals active BMP signaling in similar target cells. Our data suggest that BMP signaling is an attractive therapeutic target for interfering with structural changes in spondyloarthropathy either as an alternative or complementary approach to current antiinflammatory treatments.
关节融合是人类脊柱关节病致残的主要原因。在此我们报告，在DBA/1小鼠的一种自发性关节炎模型中，这一过程部分重现了胚胎期软骨内骨形成。骨形态发生蛋白（BMP）信号似乎是参与这一病理级联反应的关键分子途径。作为BMP拮抗剂的头蛋白的全身基因转移，在小鼠模型中作为预防和治疗策略均有效，从机制上干扰了疾病进程早期的韧带祖细胞增殖。对脊柱关节病患者韧带活检组织中磷酸化smad1/5进行免疫组织化学染色，显示在类似靶细胞中有活跃的BMP信号。我们的数据表明，BMP信号作为干扰脊柱关节病结构改变的一种治疗靶点很有吸引力，可作为当前抗炎治疗的替代或补充方法。
