TY - JOUR

T1 - Proteoglycan synthesis rate as a novel method to measure blood-induced cartilage degeneration in non-haemophilic and haemophilic rats

AU - Pulles, Astrid E.

AU - Vøls, Kåre K.

AU - Christensen, Kristine R.

AU - Coeleveld, Katja

AU - Hansen, Axel K.

AU - van Vulpen, Lize F.D.

AU - Petersen, Maj

AU - Mastbergen, Simon C.

AU - Roepstorff, Kirstine

AU - Schutgens, Roger E.G.

AU - Kjelgaard-Hansen, Mads

AU - Lafeber, Floris P.J.G.

N1 - Publisher Copyright: © 2020 The Authors. Haemophilia published by John Wiley & Sons Ltd

PY - 2020

Y1 - 2020

N2 - 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 35Sulphate incorporation (35SO4 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 35SO4 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 35SO4 2− assay in a haemophilic rat model, establishing this assay as a novel method to study blood-induced cartilage damage.

AB - 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 35Sulphate incorporation (35SO4 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 35SO4 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 35SO4 2− assay in a haemophilic rat model, establishing this assay as a novel method to study blood-induced cartilage damage.

KW - arthropathies

KW - cartilage

KW - experimental animal models

KW - haemarthrosis

KW - haemophilia

U2 - 10.1111/hae.13969

DO - 10.1111/hae.13969

M3 - Journal article

C2 - 32212362

AN - SCOPUS:85082195785

VL - 26

SP - e88-e96

JO - Haemophilia, Supplement

JF - Haemophilia, Supplement

SN - 1355-0691

IS - 3

ER -