在原发性或特发性骨关节炎(OA)中,目前尚不清楚哪些因素会导致关节软骨细胞活性从合成代谢前转变为分解代谢前.事实上,关于原发性OA的病因存在争议,机械性或炎性。软骨细胞是机械敏感细胞,在称为机械传导的过程中,将机械刺激整合到细胞反应中。机械传导的发生是由于机械传感器的激活,一组专门的蛋白质,将物理信号转化为细胞内信号级联。中等水平的机械负荷维持正常组织功能并具有抗炎作用。相比之下,机械性超负荷或低负荷可能导致软骨破坏和促炎细胞因子表达增加.同时,机械转导过程可以通过促炎和抗炎的可溶性介质来调节和调节,都是本地的(同一关节的细胞,即,软骨细胞本身,浸润的巨噬细胞,成纤维细胞或破骨细胞)和全身性(来自其他组织,例如,脂肪因子)。因此,在OA中,机械传导的复杂过程可能会改变,因此,保留软骨的软骨细胞对机械信号具有不同的敏感性,在OA条件下,健康软骨中阳性转导的机械刺激可能会变得有害。这篇综述旨在概述软骨细胞的生化暴露如何改变这些细胞中重要的机械转导过程。四个主要的机械传感器,即,整合素,Ca2+通道,主要纤毛和Wnt信号(规范和非规范)为目标。对于这些机械传感器中的每一个,对健康或OA条件下对机械负荷的反应进行了简要总结,然后对已发表的著作进行了简要概述,这些著作着重于生化因素对机械传导途径的进一步调节。总之,本文讨论并探讨了在健康和原发性OA中,生物介质如何在机械负荷下影响软骨细胞的差异行为。
In primary or idiopathic osteoarthritis (OA), it is unclear which factors trigger the shift of articular chondrocyte activity from pro-anabolic to pro-catabolic. In fact, there is a controversy about the aetiology of primary OA, either mechanical or inflammatory. Chondrocytes are mechanosensitive cells, that integrate mechanical stimuli into cellular responses in a process known as mechanotransduction. Mechanotransduction occurs thanks to the activation of mechanosensors, a set of specialized proteins that convert physical cues into intracellular signalling cascades. Moderate levels of mechanical loads maintain normal tissue function and have anti-inflammatory effects. In contrast, mechanical over- or under-loading might lead to cartilage destruction and increased expression of pro-inflammatory cytokines. Simultaneously, mechanotransduction processes can regulate and be regulated by pro- and anti-inflammatory soluble mediators, both local (cells of the same joint, i.e., the chondrocytes themselves, infiltrating macrophages, fibroblasts or osteoclasts) and systemic (from other tissues, e.g., adipokines). Thus, the complex process of mechanotransduction might be altered in OA, so that cartilage-preserving chondrocytes adopt a different sensitivity to mechanical signals, and mechanic stimuli positively transduced in the healthy cartilage may become deleterious under OA conditions. This review aims to provide an overview of how the biochemical exposome of chondrocytes can alter important mechanotransduction processes in these cells. Four principal mechanosensors, i.e., integrins, Ca2+ channels, primary cilium and Wnt signalling (canonical and non-canonical) were targeted. For each of these mechanosensors, a brief summary of the response to mechanical loads under healthy or OA conditions is followed by a concise overview of published works that focus on the further regulation of the mechanotransduction pathways by biochemical factors. In conclusion, this paper discusses and explores how biological mediators influence the differential behaviour of chondrocytes under mechanical loads in healthy and primary OA.