Proof of concept: enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells
Proof of concept: enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells
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DOI：
10.1136/annrheumdis-2013-203643
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发表时间：
2014-02-01
影响因子：
27.4
通讯作者：
Elewaut, Dirk
中科院分区：
文献类型：
--
作者：
Jacques, Peggy;Lambrecht, Stijn;Elewaut, Dirk
目的脊柱关节炎（SpA）是以外周关节炎和轴性关节炎为特征的疾病。外周型SpA的特征是附着点炎的发展，最典型的是跟腱和足底筋膜，以及新骨形成。这项研究是为了解开机制，导致附着点炎和新骨形成的临床前模型SpA.Results首先，我们证明，TNF δ ARE小鼠表现出典型的炎症特征，高度联想到SpA。第一个炎症迹象是在附着点发现的。重要的是，附着点炎在成熟T和B细胞存在或不存在的情况下同样发生，强调了基质细胞的重要性。与负重对照组相比，TNF δ ARE小鼠后肢去负荷显著抑制了跟腱炎症。Erk 1/2信号在机械传导相关炎症中起着至关重要的作用。此外，新骨形成强烈促进附着点的生物力学应力和inflammation. Conclusions的程度相关，这些研究结果提供了一个正式的证明的概念，机械应变驱动附着点炎症和新骨形成在SpA。
Objectives Spondyloarthritides (SpA) are characterised by both peripheral and axial arthritis. The hallmarks of peripheral SpA are the development of enthesitis, most typically of the Achilles tendon and plantar fascia, and new bone formation. This study was undertaken to unravel the mechanisms leading towards enthesitis and new bone formation in preclinical models of SpA.Results First, we demonstrated that TNF Delta ARE mice show typical inflammatory features highly reminiscent of SpA. The first signs of inflammation were found at the entheses. Importantly, enthesitis occurred equally in the presence or absence of mature T and B cells, underscoring the importance of stromal cells. Hind limb unloading in TNF Delta ARE mice significantly suppressed inflammation of the Achilles tendon compared with weight bearing controls. Erk1/2 signalling plays a crucial role in mechanotransduction-associated inflammation. Furthermore, new bone formation is strongly promoted at entheseal sites by biomechanical stress and correlates with the degree of inflammation.Conclusions These findings provide a formal proof of the concept that mechanical strain drives both entheseal inflammation and new bone formation in SpA.