韧带骨化是引起强直性脊柱炎（AS）患者关节强直的重要原因，而炎症可能是触发韧带骨化的重要因素。炎症相关因子白细胞介素-6（IL-6）的表达水平在AS病人血清中显著升高且与疾病的活动度有相关性。申请人前期研究发现糖蛋白130（gp130）、信号转导和转录活化蛋白1（STAT1）、3ˊ-磷酸腺苷5ˊ-磷酸硫酸合成酶2（PAPSS2）在AS FLL细胞中表达量显著上调。同时AS病人韧带组织中JAK1和STAT1的磷酸化水平显著升高。而有报道显示IL-6和PAPSS2能够促进具有成骨潜力细胞的增殖、钙化和成骨。所以本项目将通过体内和体外实验研究IL-6和PAPSS2促进韧带骨化的作用及IL-6通过gp130/JAK1/STAT1信号通路调控PAPSS2表达的机制。本研究可为揭示AS的致病机理提供新思路，为AS的治疗提供新靶点。

Ossification of ligament is an important cause of ankylosis in ankylosing spondylitis (AS) patients. Inflammation might trigger the ossification of ligament in AS. The levels of interleukin-6 ( IL-6 ) in serum of AS patients were significantly increased and correlated with the disease activity. Our previous studies found that the expression of glycoprotein 130, signal transducer and activator of transcription 1(STAT1) and 3ˊ-phosphoadenosine 5ˊ-phosphsulfate synthetase 2 ( PAPSS2 ) in AS fibroblast like ligament(FLL) cells increased significantly. Meanwhile, the phosphorylation levels of JAK1 and STAT1 in the ligament tissue of AS patients were significantly increased. It has been reported that IL-6 and PAPSS2 can promote proliferation, calcification and osteogenesis of cells with osteogenic potential. So, we will study the function of IL-6 and PAPSS2 in promoting ligament ossification of AS patients and the mechanism of PAPSS2 expression regulated by IL-6 through gp130 /JAK1 / STAT1 signaling pathway using in vivo and in vitro experimental method. These studies may offer new thinking for pathogenesis and new target for treatment of AS.