TY - JOUR

T1 - Rapid inflammation and early degeneration of bone and cartilage revealed in a time-course study of induced haemarthrosis in haemophilic rats

AU - Christensen, Kristine Rothaus

AU - Kjelgaard-Hansen, Mads

AU - Nielsen, Lise Nikolic

AU - Wiinberg, Bo

AU - Althoehn, Frederik Alexander

AU - Poulsen, Niels Bloksgaard

AU - Vols, Kare Kryger

AU - Thyme, Anders Popp

AU - Lovgren, Karin Maria

AU - Hansen, Axel Kornerup

AU - Roepstorff, Kirstine

PY - 2019

Y1 - 2019

N2 - ObjectivesDetailed knowledge of the sequential cell and tissue responses following haemarthrosis is important for a deep understanding of the pathological process initiated upon extensive bleeding into the joint causing haemophilic arthropathy (HA). The underlying pathobiology driving haemarthrosis towards HA has been difficult to establish in detail, although animal models have shed light on some processes. Previous studies have focused on a single or a few distant time points and often only characterizing one tissue type of the joint. The objective of this study was, therefore, to carefully map early onset of synovitis and HA following induced haemarthrosis.MethodsOne hundred and thirty haemophilia A rats were subjected to induced haemarthrosis or a sham procedure in full anaesthesia and euthanized from 30 min to 7 days after the procedure. Pathological changes of the joints were visualized using micro-computed tomography, histology and immunohistochemistry.ResultsSynovitis developed within 24 h and was dominated by myeloid cell infiltrations. Cartilage and bone pathology were evident as early as 48–96 h after haemarthrosis, and the pathology rapidly progressed with extensive periosteal bone formation and formation of subchondral cysts.ConclusionFast, extensive and simultaneous cartilage and bone degeneration developed shortly after haemarthrosis, as shown by the detailed mapping of the early pathogenesis of HA. The almost immediate loss of cartilage and the pathological bone turnover suggest a direct influence of blood on these processes and are unlikely to be attributed simply to an indirect effect of inflammation.

AB - ObjectivesDetailed knowledge of the sequential cell and tissue responses following haemarthrosis is important for a deep understanding of the pathological process initiated upon extensive bleeding into the joint causing haemophilic arthropathy (HA). The underlying pathobiology driving haemarthrosis towards HA has been difficult to establish in detail, although animal models have shed light on some processes. Previous studies have focused on a single or a few distant time points and often only characterizing one tissue type of the joint. The objective of this study was, therefore, to carefully map early onset of synovitis and HA following induced haemarthrosis.MethodsOne hundred and thirty haemophilia A rats were subjected to induced haemarthrosis or a sham procedure in full anaesthesia and euthanized from 30 min to 7 days after the procedure. Pathological changes of the joints were visualized using micro-computed tomography, histology and immunohistochemistry.ResultsSynovitis developed within 24 h and was dominated by myeloid cell infiltrations. Cartilage and bone pathology were evident as early as 48–96 h after haemarthrosis, and the pathology rapidly progressed with extensive periosteal bone formation and formation of subchondral cysts.ConclusionFast, extensive and simultaneous cartilage and bone degeneration developed shortly after haemarthrosis, as shown by the detailed mapping of the early pathogenesis of HA. The almost immediate loss of cartilage and the pathological bone turnover suggest a direct influence of blood on these processes and are unlikely to be attributed simply to an indirect effect of inflammation.

KW - arthropathy

KW - subchondral cyst

KW - haemophilia

KW - immunohistochemistry

KW - inflammation

KW - rattus

KW - synovitis

KW - X-ray computed tomography

U2 - 10.1093/rheumatology/key186

DO - 10.1093/rheumatology/key186

M3 - Journal article

C2 - 29982826

VL - 58

SP - 588

EP - 599

JO - Rheumatology

JF - Rheumatology

SN - 1462-0324

IS - 4

ER -