Cadherin-11 involves in synovitis and increases the migratory and invasive capacity of fibroblast-like synoviocytes of osteoarthritis

Abstract

Objective: To detect the expression of cadherin-11 and its correlation with synovitis in osteoarthritis (OA), to explore the mechanism of over expression of cadherin-11 and its role in migratory or invasive capacity of fibroblast-like synoviocytes (FLS).

Methods: Synovitis severity was recorded according to Krenn's scoring system in 25 osteoarthritis patients undergoing total knee arthroplasty. Cadherin-11 expression in OA synoviums and its correlation with synovitis score and systemic inflammation markers were explored. After induction with Interleukin-1 beta (IL-1β) or tumor necrosis factor-alpha (TNF-α),cadherin-11 expression on OA FLS was assessed by qPCR and western blot,the capacity of migration and invasion of OA FLS was tested by transwell assay, and matrix metalloproteinase-2 production was assessed with ELISA as cadherin-11 expression was up regulated after infection with cadherin-11 cDNA-containing lentivirus, also when cadherin-11 expression was knocked down after infection with cadherin 11 shRNA containing lentivirus.

Results: Cadherin-11 expression in OA synovium showed significant differences among different grades of synovitis. Cadherin-11 in the lining layer was positively correlated with hyperplasia of the lining layer, density of the resident cells, inflammatory infiltrate, total synovitis score and D-dimer. Cadherin-11 in the sublining layer was positively correlated with the density of the resident cells, inflammatory infiltrate, total synovitis score and erythrocyte sedimentation rate. IL-1β or TNF-α could up-regulate cadherin-11 expression on OA FLS at transcriptional and protein level. Over expression of cadherin-11 increased migratory or invasive capacity of OA FLS, while cadherin-11 knock down reduced migratory or invasive capacity and MMP-2 production in OA FLS.

Conclusion: The over expression of cadherin-11 in osteoarthritis is positively correlated with synovitis severity, and can be driven by proinflammatory cytokines on OA FLS; cadherin-11 increases migratory or invasive capacity and MMP-2 production of fibroblast-like synoviocytes of osteoarthritis.

Keywords: Cadherin-11; Interleukin-1 beta; Osteoarthritis; Synovitis; Tumor necrosis factor-alpha.