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 - Funding Information:
Novo Nordisk A/S partially funded the study.
Publisher Copyright:
© 2020 The Authors. Haemophilia published by John Wiley & Sons Ltd
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/5/1
Y1 - 2020/5/1
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
UR - http://www.scopus.com/inward/record.url?scp=85082195785&partnerID=8YFLogxK
U2 - 10.1111/hae.13969
DO - 10.1111/hae.13969
M3 - Article
C2 - 32212362
SN - 1351-8216
VL - 26
SP - e88-e96
JO - Haemophilia
JF - Haemophilia
IS - 3
ER -