Increased level of heme oxygenase-1 in rheumatoid arthritis synovial fluid

Abstract

We investigated the expression and localization of heme oxygenase-1 (HO-1) in synovial fluid and synovial tissue, and examined the stimulation of HO-1 production in rheumatoid synovial fibroblasts (RASFs). Synovial fluid samples were obtained from knee joints of 20 rheumatoid arthritis (RA) and 20 osteoarthritis (OA) patients, and concentration of HO-1 and matrix metalloproteinase-3 (MMP-3) were measured by enzyme-linked immunosorbent assay (ELISA). Synovial tissues obtained from RA or OA patients during total knee arthroplasty (TKA) were used for immunohistochemical analysis of HO-1. HO-1 production by RASFs in response to various cytokines was examined by ELISA. HO-1 levels in synovial fluid were higher in the RA group than in the OA group with significant difference (P < 0.001), and correlated with serum C-reactive protein (CRP) level (r = 0.80, P < 0.01) in the RA group. Higher levels of HO-1 were seen in the RA-L group (Larsen grade III-V) than in the RA-E (Larsen grade 0-II) group (P < 0.001). There was weak correlation between the levels of HO-1 protein and MMP-3 in synovial fluid in the RA group (r = 0.31, P < 0.01), while no positive correlation was observed in OA. Positive immunoreaction for HO-1 was observed in cells of synovial tissue including synovial fibroblasts and cells in synovial pannus. HO-1 protein levels in cultured media of RASFs were increased by stimulation by interleukin-1β at 6 h and tumor necrosis factor-alpha at 12 h, but suppressed by interferon-gamma at 12 and 24 h. These results indicated that HO-1 expression in synovial tissue might be stimulated by inflammatory cytokines. The correlation of HO-1 concentration in synovial fluid with serum CRP and MMP-3 in joint fluid indicated that HO-1 might be useful as a marker of joint inflammation in RA patients.

Serum Heme Oxygenase-1 and BMP-7 Are Potential Biomarkers for Bone Metabolism in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis

“…None of serum levels of HO-1, BMP-7, and Runx2 was associated with inflammatory markers or disease activity in any of the patient groups under investigation. In contrast to our data, Kitamura et al found that HO-1 levels in RA synovial fluids correlated with serum levels of CRP [ 4 ]. A previous study on either RA or OA revealed that HO-1 significantly reduced the production of proinflammatory cytokines [ 4 , 9 , 13 ].…”

“…In contrast to our data, Kitamura et al found that HO-1 levels in RA synovial fluids correlated with serum levels of CRP [ 4 ]. A previous study on either RA or OA revealed that HO-1 significantly reduced the production of proinflammatory cytokines [ 4 , 9 , 13 ]. In line with our results, Korkosz et al found no correlation between the serum BMP-7 concentrations and either ESR or CRP in patients with AS [ 34 ].…”

“…HO-1 plays a crucial role in cytoprotection. Some studies described increased levels of HO-1 in the synovial tissue, synovial fluid, and synovial cells of patients with RA compared to those in controls [ 4 , 20 , 21 ]. Data on serum levels of HO-1 in patients with RA or AS are scarce.…”

Heme Oxygenase-1 Regulates the Progression of K/BxN Serum Transfer Arthritis

“…An association of HO-1 promoter polymorphism with rheumatoid arthritis (RA) has been reported [4] and patients with the SS genotype, resulting in a higher HO-1 expression, may have a better long-term radiographic outcome despite disease activity [5]. HO-1 protein is expressed in synovial tissues of RA patients [6] and its presence in synovial fluid may be a marker of joint inflammation [7] Nevertheless, treatment of RA patients with tumor necrosis factor α (TNF-α) antagonists may block the TNF-α-dependent suppression of HO-1 expression in peripheral blood cells, resulting in amelioration of inflammation [8].…”

Local gene delivery of heme oxygenase-1 by adeno-associated virus into osteoarthritic mouse joints exhibiting synovial oxidative stress

“…HO-1 exhibits multiple beneficial properties including antioxidant, anti-inflammatory and cytoprotective functions and is often endogenously induced by various stress stimuli 18,19,43,44 . It has been detected in human OA synovium, cartilage and synovial fluids 42e44 .…”