Osteoarthritis (OA) is no longer considered a cartilage-centric disease with remodelling of other joint tissues now recognized. While understudied, entheseal pathology is considered a secondary OA feature. A pivotal role for proteinase-activated receptor 2 (PAR2) in OA has been demonstrated previously in cartilage and subchondral bone at early time points, however the entheseal role of PAR2 has not been reported.

OA was induced by destabilization of the medial meniscus (DMM) in wild type (WT) and PAR2 deficient (KO) animals. At 4 weeks and one year post surgery, knee joints were harvested for histological analysis. Medial collateral ligament (MCL) width was measured by 2D planimetry analysis. Immunohistochemistry was used to characterize the MCL and anterior cruciate ligament (ACL). Data were expressed as mean±SEM (n=4–6/group) and analysed using Student's t-test, with p<0.05 as the criterion of significance.

MCL width increased between 4 weeks and 1 year in WT DMM (0.24 ±0.07 vs 0.40 ±0.008mm respectively, p<0.001). Interestingly, a significant reduction in MCL was observed in KO compared with WT at 1 year (0.23 ±0.005 vs 0.40 ±0.008mm respectively, p <0.001) post-DMM. Further characterization of DMM WT MCL and ACL at 4 weeks showed the presence of F4/80⁺ cells in addition to IL-33 and histamine. At one year post-surgery, a cellular infiltrate was observed in MCL DMM WT but absent in KO mice. Histological evaluation revealed an absence of F4/80⁺ cells but the presence of a PAR2⁺ population, subsequently identified as hypertrophic-like chondrocytes (RUNX2) and chondrocytes-like cells (SOX9).

Deletion of PAR2 affords long-term protection against ligament remodelling and demonstrates a critical role for this receptor in both OA joint pathology and ligament injuries. While PAR2 appears to be a credible therapeutic target in OA entheseal pathology, further understanding of the molecular mechanism regulated by this receptor will be required.

INTRODUCTION

Prosthetic joint related-infections (PJRI) are severe complications in orthopaedic surgery. Staphylococcus aureus and Staphylococcus epidermidis are the most commonly isolated pathogens from implants (1). The variable antimicrobial susceptibility found in these microorganisms, makes it necessary to perform individual susceptibility studies in order to select the best antibiotic combination for clinical management (2).