Arthritis Research Unit, Laboratory for Skeletal Development and Joint Disorders, K.U. Leuven, Leuven, Belgium.
Ther Adv Musculoskelet Dis. 2012 Aug;4(4):293-9. doi: 10.1177/1759720X12444175.
Ankylosing spondylitis (AS), the best-known form of spondyloarthritis (SpA), is a remodelling arthritis characterized by chronic inflammation and bone formation. Ankylosis of the axial skeleton and sacroiliac joints leads to an impairment of spinal mobility, progressive spinal fusion and an increased risk of spinal fractures. The nature of the relationship between inflammation and new bone formation in AS has been controversial and questions remain as to whether there is a direct relationship between inflammation and new bone formation. Like others, we have hypothesized that the molecular pathways underlying ankylosis recapitulate the process of endochondral bone formation and that bone morphogenetic proteins (BMPs) play a key role in this process in AS. Furthermore, we discuss the entheseal stress hypothesis, which proposes that inflammation and ankylosis are linked but largely independent processes, and consider observations from mouse models and other human diseases which also imply that biomechanical factors contribute to the pathogenesis of AS. As current therapeutics, such as tumour necrosis factor inhibitors do not impede disease progression and ankylosis in AS, it is the pathways discussed in this review that are the now the focus for the identification of future drug targets.
强直性脊柱炎（AS），即最常见的脊柱关节炎（SpA）形式，是一种以慢性炎症和骨形成为特征的骨改建关节炎。轴性骨骼和骶髂关节的强直会导致脊柱活动度受损、进行性脊柱融合以及脊柱骨折风险增加。AS 中炎症和新骨形成之间的关系性质一直存在争议，并且仍存在炎症和新骨形成之间是否存在直接关系的问题。和其他人一样，我们假设，在脊柱强直中，新骨形成的分子途径再现了软骨内骨形成的过程，并且骨形态发生蛋白（BMPs）在该过程中发挥关键作用。此外，我们还讨论了腱附着点应激假说，该假说提出炎症和强直是相互关联但在很大程度上是独立的过程，并考虑了来自小鼠模型和其他人类疾病的观察结果，这些结果也表明生物力学因素有助于 AS 的发病机制。由于目前的治疗方法，如肿瘤坏死因子抑制剂并不能阻止 AS 中的疾病进展和强直，因此，正是本综述中讨论的途径成为了确定未来药物靶点的重点。
