School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK.
Biomechanics and Bioengineering Centre Versus Arthritis, School of Biosciences, Cardiff University, Cardiff, CF10 3AX, UK.
Histochem Cell Biol. 2020 Nov;154(5):521-531. doi: 10.1007/s00418-020-01918-1. Epub 2020 Sep 15.
Mechanically mediated joint degeneration and cartilage dyshomeostasis is implicated in highly prevalent diseases such as osteoarthritis. Increasingly, MicroRNAs are being associated with maintaining the normal state of cartilage, making them an exciting and potentially key contributor to joint health and disease onset. Here, we present a summary of current in vitro and in vivo models which can be used to study the role of mechanical load and MicroRNAs in joint degeneration, including: non-invasive murine models of PTOA, surgical models which involve ligament transection, and unloading models based around immobilisation of joints or removal of load from the joint through suspension. We also discuss how zebrafish could be used to advance this field, namely through the availability of transgenic lines relevant to cartilage homeostasis and the ability to accurately map strain through the cartilage, enabling the response of downstream MicroRNA targets to be followed dynamically at a cellular level in areas of high and low strain.
机械介导的关节退化和软骨动态平衡失调与骨关节炎等高发疾病有关。越来越多的 MicroRNAs 与维持软骨的正常状态有关,这使它们成为关节健康和疾病发生的一个令人兴奋的、潜在的关键因素。在这里,我们总结了目前可用于研究机械负荷和 MicroRNAs 在关节退化中的作用的体外和体内模型,包括:PTOA 的非侵入性小鼠模型、涉及韧带切断的手术模型,以及基于关节固定或通过关节悬吊去除关节负荷的卸载模型。我们还讨论了斑马鱼如何用于推进这一领域,即通过与软骨动态平衡相关的转基因系的可用性,以及通过软骨准确绘制应变图的能力,使下游 MicroRNA 靶标的反应能够在高应变和低应变区域以细胞水平动态跟踪。