强直性脊柱炎(AS)致残的两大原因为炎症性腰背痛和中轴骨骼关节强直。研究证明脊柱强直与炎症相对独立，炎症的控制并不能抑制脊柱强直的进展。异位成骨导致脊柱强直的机制尚不清楚。研究发现，炎症环境下Wnt蛋白及其介导的信号转导参与脊柱异位成骨的发生。我们前期实验发现非经典通路Wnt蛋白及PKCδ在患者手术标本中高表达；在细胞模型中TNF-α能刺激Wnt蛋白表达与分泌，并促进成骨分化，且该作用与PKCδ有关。由此我们提出科学假设：在AS的病理过程中，TNF-α诱导炎症细胞表达分泌非经典通路Wnt蛋白，并激活脊柱韧带及附着点处细胞内Wnt/PKCδ信号通路，促进其成骨分化与矿化，导致脊柱强直。本课题拟在细胞模型中探讨Wnt/PKCδ在TNF-α刺激下促进成骨分化的分子机制，并建立动物模型验证Wnt/PKCδ在异位成骨过程中的作用。本研究有望揭示AS异位新骨形成的机制，为其防治提供新的思路和靶点。

Ankylosing spondylitis (AS) is an autoimmune chronic connective tissue disease characterized by chronic inflammation and bone formation. Pain and Ankylosis of the axial skeleton are the two key factors leading to disability. The nature of the relationship between inflammation and new bone formation in AS has been controversial. New bone formation is more likely to be an uncoupling process of inflammation in AS. Wnt protein family has been reported to play a key role in ectpoic bone formation in AS. In previous studies, we observed noncannonical Wnts and PKCδ expression in samples collected in AS correction surgeries, and Wnt/PKCδ was activated by TNF-α and involved in osteogenesis in inflammatory environment in an in vitro study. We therefore hypothezie that TNF-α induced Wnt/PKCδ activation is an important regulatory mechanism of ectopic bone formation in the ligaments and entheses causing ankylosis in AS. To prove this hypothesis, we design the current study, including in vitro study to investigate the molecular regulatory mechanism of Wnt/PKCδ inducing ectopic osteogenesis and in vivo study with an AS animal model to validate the role of Wnt/PKCδ in ankylosis. The findings of the current study would provide more insight of AS and help with identification of noval treatment target.