The pathophysiology of osteoarthritis
The pathophysiology of osteoarthritis
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DOI：
10.1007/bf03327357
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发表时间：
2003-10-01
影响因子：
4
通讯作者：
Lapadula, G
中科院分区：
文献类型：
--
作者：
Iannone, F;Lapadula, G
骨关节炎（OA）是一种复杂的疾病，其发病机制包括生物力学和代谢因素的作用，这些因素改变了关节软骨和软骨下骨的组织稳态，决定了破坏性过程优于生产性过程。细胞/细胞外基质（ECM）相互作用在关节软骨病理生理中起着关键作用，这种相互作用是由细胞表面整合素介导的。在生理环境中，整合素调节细胞/ECM信号，对调节生长和分化以及维持软骨稳态至关重要。在CIA期间，整合素的异常表达改变了细胞/ECM信号传导并改变了软骨细胞的合成，随后破坏性细胞因子与调节因子的失衡。IL-1， tnf - α和其他促分解代谢细胞因子激活软骨基质的酶降解，并且不能通过适当的抑制剂合成来平衡。参与ECM分解的主要酶是金属蛋白酶（MMPs），其通过扩增级联顺序激活。MMP活性被组织抑制剂（TIMPs）部分抑制，与OA软骨中MMP的合成相比，TIMPs的合成较低。令人感兴趣的是tgf - β、IFG、BMP、NGF等生长因子的作用，它们不仅能修复分解代谢因子诱导的组织损伤，而且在OA发病机制中发挥着重要作用。
Osteoarthritis (OA) is a complex disease whose pathogenesis includes the contribution of biomechanical and metabolic factors which, altering the tissue homeostasis of articular cartilage and subchondral bone, determine the predominance of destructive over productive processes. A key role in the pathophysiology of articular cartilage is played by cell/extra-cellular matrix (ECM) interactions, which are mediated by cell surface integrins. In a physiologic setting, integrins modulate cell/ECM signaling, essential for regulating growth and differentiation and maintaining cartilage homeostasis. During CIA, abnormal integrin expression alters cell/ECM signaling and modifies chondrocyte synthesis, with the following imbalance of destructive cytokines over regulatory factors. IL-1, TNF-alpha and other pro-catabolic cytokines activate the enzymatic degradation of cartilage matrix and are not counterbalanced by adequate synthesis of inhibitors. The main enzymes involved in ECM breakdown are metalloproteinases (MMPs), which are sequentially activated by an amplifying cascade. MMP activity is partially inhibited by the tissue inhibitors of MMPs (TIMPs), whose synthesis is low compared with MMP production in OA cartilage. Intriguing is the role of growth factors such as TGF-beta, IFG, BMP, NGF, and others, which do not simply repair the tissue damage induced by catabolic factors, but play an important role in OA pathogenesis.