title: Synovial fluid hyaluronan mediates MSC attachment to cartilage, a potential novel mechanism contributing to cartilage repair in osteoarthritis using knee joint distraction.
abstract: OBJECTIVE
  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 >9 MDa 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.
authors.affiliation: Faculty of Medicine, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, West Yorkshire, UK.
authors.forename: Thomas G
authors.identifier: http://orcid.org/0000-0003-4444-0318
authors.initials: TG
authors.lastname: Baboolal
authors.affiliation: Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Mastbergen
authors.affiliation: Faculty of Medicine, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, West Yorkshire, UK NIHR-Leeds Musculoskeletal and Biomedical Research Unit, Chapel Allerton, Leeds Teaching Hospital Trust, Leeds, West Yorkshire, UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Jones
authors.affiliation: Department of Trauma and Orthopaedics, Chapel Allerton, Leeds Teaching Hospital Trust, Leeds, West Yorkshire, UK.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Calder
authors.affiliation: Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Floris P J G
authors.initials: FP
authors.lastname: Lafeber
authors.affiliation: Faculty of Medicine, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, West Yorkshire, UK NIHR-Leeds Musculoskeletal and Biomedical Research Unit, Chapel Allerton, Leeds Teaching Hospital Trust, Leeds, West Yorkshire, UK.
authors.forename: Dennis
authors.initials: D
authors.lastname: McGonagle
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000473:pathology; D002358:Cartilage, Articular / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D004195:Disease Models, Animal; D004285:Dogs; D016267:External Fixators; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008970:Molecular Weight; D019637:Orthopedic Procedures / Q000379:methods; D020370:Osteoarthritis, Knee / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D013582:Synovial Fluid / Q000502:physiology*; D046509:Tissue Culture Techniques; D014945:Wound Healing / Q000502:physiology
chemical_list: D006820:Hyaluronic Acid
keywords: Knee Osteoarthritis; Orthopedic Surgery; Osteoarthritis; Synovial fluid