Proteoglycan synthesis rate as a novel method to measure blood‐induced cartilage degeneration in non‐haemophilic and haemophilic rats

INTRODUCTION: Haemophilic animal models are used to study blood‐induced cartilage damage, but quantitative and sensitive outcome measures are needed. AIM: To develop a novel quantitative method for detecting early cartilage degeneration in a haemophilic rat model of blood‐induced joint damage. METHODS: The (35)Sulphate incorporation ((35)SO(4) (2−) 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 (35)SO(4) (2−) assay, with the contralateral knee as control. RESULTS: 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. CONCLUSION: For the first time, early changes in cartilage matrix synthesis upon blood exposure were quantified with the (35)SO(4) (2−) assay in a haemophilic rat model, establishing this assay as a novel method to study blood‐induced cartilage damage.