Department of Rheumatology & Clinical Immunology, University Medical Center (UMC) Utrecht, Utrecht University, Utrecht, The Netherlands.
Van Creveldkliniek, UMC Utrecht, Utrecht University, Utrecht, The Netherlands.
Haemophilia. 2020 May;26(3):e88-e96. doi: 10.1111/hae.13969. Epub 2020 Mar 25.
Haemophilic animal models are used to study blood-induced cartilage damage, but quantitative and sensitive outcome measures are needed.
To develop a novel quantitative method for detecting early cartilage degeneration in a haemophilic rat model of blood-induced joint damage.
The Sulphate incorporation ( SO assay) was applied to tibial and patellar cartilage of wild-type rats to quantify baseline proteoglycan synthesis and to evaluate the effect of 4-day blood exposure in vitro. Next, haemarthrosis was induced in 39 FVIII-deficient rats and characterized by changes in knee joint diameter and development of bone pathology (using micro-CT). Four- and 16-day posthaemarthrosis proteoglycan synthesis rate (PSR) was assessed using the SO assay, with the contralateral knee as control.
In vitro, a decrease in PSR in tibial and patellar cartilage was demonstrated following blood exposure. In vivo, joint diameter and development of bone pathology confirmed successful induction of haemarthrosis. In the blood-exposed knee, tibial and patellar PSR was inhibited 4 and 16 days after induced haemarthrosis. Interestingly, at day 16 the proteoglycan synthesis in the contralateral knee was also inhibited to an extent correlating with that of the blood-exposed knee.
For the first time, early changes in cartilage matrix synthesis upon blood exposure were quantified with the SO assay in a haemophilic rat model, establishing this assay as a novel method to study blood-induced cartilage damage.
血友病动物模型被用于研究血液引起的软骨损伤，但需要定量和敏感的结果测量方法。
开发一种新的定量方法，用于检测血液引起的关节损伤血友病大鼠模型中的早期软骨退变。
硫酸盐掺入（SO 测定）应用于野生型大鼠的胫骨和髌骨软骨，以定量基线蛋白聚糖合成，并评估体外 4 天血液暴露的效果。接下来，在 39 只 FVIII 缺乏的大鼠中诱导关节积血，并通过膝关节直径变化和骨病理学发展（使用 micro-CT）进行特征描述。使用 SO 测定法评估关节积血后 4 天和 16 天的蛋白聚糖合成率（PSR），以对侧膝关节作为对照。
在体外，血液暴露后观察到胫骨和髌骨软骨 PSR 下降。在体内，关节直径和骨病理学的发展证实了关节积血的成功诱导。在血液暴露的膝关节中，关节积血后 4 天和 16 天，胫骨和髌骨 PSR 受到抑制。有趣的是，在第 16 天，对侧膝关节的蛋白聚糖合成也受到抑制，其程度与血液暴露膝关节的抑制程度相关。
首次使用 SO 测定法在血友病大鼠模型中定量检测血液暴露后软骨基质合成的早期变化，确立了该测定法作为研究血液引起的软骨损伤的新方法。
