Synovial fluid hyaluronan mediates MSC attachment to cartilage, a potential novel mechanism contributing to cartilage repair in osteoarthritis using knee joint distraction

Abstract

ObjectivesKnee 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.MethodsAttachment 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.ResultsOsteoarthritic-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.ConclusionsThese 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.

Platelet lysate enhances synovial fluid multipotential stromal cells functions: Implications for therapeutic use

“…Since SF-MSCs have the advantage of direct access to the site of injury without the need to breach the subchondral plate [36], combining PL with SF-MSCs might be relevant for early cartilage repair. Our results showed that PL maintained the in vitro phenotype in agreement with the recommendation of the ISCT [37].…”

Comparison of Arthroscopic and Conservative Treatments for Knee Osteoarthritis: A 5-Year Retrospective Comparative Study

“…[1][2][3] There is still no curative treatment for KOA and only a small number of limited treatments, which aim to reduce pain and control inflammation to improve function. The treatment of KOA in the early stages includes physical therapy, [4][5][6] pain relief by nonsteroidal anti-inflammatory drugs, 7 cell-based therapy, 8,9 and intra-articular injection of hyaluronan or corticosteroids. 10 However, these therapies provide only temporary clinical symptom relief and do not restore cartilaginous, meniscal, and ligamentous function.…”

The molecular profile of synovial fluid changes upon joint distraction and is associated with clinical response in knee osteoarthritis

“…These studies suggest that, by temporarily offloading the joint, KJD might somehow be responsible for 'priming' the joint to enable intrinsic cartilaginous repair. The biological mechanisms which underlie such a response are not understood but may include changes in the peri-articular bone and enhanced mesenchymal stem cell attachment to the damaged joint surface 19,20 . KJD is therefore an attractive mechanistic model in which to investigate potential reparative pathways and identify novel associated markers of clinical response.…”