Journal
ANNALS OF THE RHEUMATIC DISEASES
Volume 75, Issue 5, Pages 908-915Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/annrheumdis-2014-206847
Keywords
Knee Osteoarthritis; Osteoarthritis; Synovial fluid; Orthopedic Surgery
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Funding
- WELMEC, a Centre of Excellence in Medical Engineering - Wellcome Trust
- EPSRC [WT 088908/Z/09/Z]
- National Institute of Health Research via the NIHR-Leeds Musculoskeletal and Biomedical Research Unit
- Dutch Arthritis Foundation
- Engineering and Physical Sciences Research Council [EP/J017620/1, EP/N00941X/1] Funding Source: researchfish
- EPSRC [EP/J017620/1, EP/N00941X/1] Funding Source: UKRI
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Objectives Knee joint distraction (KJD) is a novel, but poorly understood, treatment for osteoarthritis (OA) associated with remarkable spontaneous' cartilage repair in which resident synovial fluid (SF) multipotential mesenchymal stromal cells (MSCs) may play a role. We hypothesised that SF hyaluronic acid (HA) inhibited the initial interaction between MSCs and cartilage, a key first step to integration, and postulate that KJD environment favoured MSC/cartilage interactions. Methods Attachment of dual-labelled SF-MSCs were assessed in a novel in vitro human cartilage model using OA and rheumatoid arthritic (RA) SF. SF was digested with hyaluronidase (hyase) and its effect on adhesion was observed using confocal microscopy. MRI and microscopy were used to image autologous dual-labelled MSCs in an in vivo canine model of KJD. SF-HA was investigated using gel electrophoresis and densitometry. Results Osteoarthritic-synovial fluid (OA-SF) and purified high molecular weight (MW) HA inhibited SF-MSC adhesion to plastic, while hyase treatment of OA-SF but not RA-SF significantly increased MSC adhesion to cartilage (3.7-fold, p<0.05) These differences were linked to the SF mediated HA-coat which was larger in OA-SF than in RA-SF. OA-SF contained >9MDa HA and this correlated with increases in adhesion (r=0.880). In the canine KJD model, MSC adhesion to cartilage was evident and also dependent on HA MW. Conclusions These findings highlight an unappreciated role of SF-HA on MSC interactions and provide proof of concept that endogenous SF-MSCs are capable of adhering to cartilage in a favourable biochemical and biomechanical environment in OA distracted joints, offering novel one-stage strategies towards joint repair.
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