This study was performed to provide evidence, albeit indirectly, as to which matrix metalloproteinases (MMPs), among the gelatinases MMP-2 and MMP-9 and the collagenases MMP-1 and MMP-13, play a more proactive role in the angiogenic process in arthritic joint. Joint fluid was collected from 33 patients with rhuematoid arthritis (RA) and osteoarthritis (OA), and protein (MMPs and vascular endothelial growth factor (VEGF)) levels were measured by ELISA, and the association of MMPs with VEGF was evaluated in joint fluid of patients with RA or OA. The levels of collagenases (total MMP-1 and total MMP-13) and gelatinases (total MMP-2 and total MMP-9) in RA joint fluid were significantly higher than those in OA fluid. Total MMP-9 levels were significantly associated with VEGF levels in RA fluids, but not in OA fluid, while total MMP-13 levels were strongly associated with VEGF levels in both RA and OA fluid. However, total MMP-2 and total MMP-1 levels were not associated with VEGF levels in either RA or OA joint fluid. Our results indirectly suggest that in RA and OA, MMP-9 and MMP-13 may play a more important role in angiogenesis than MMP-2 and MMP-1.

Clinical guidelines regarding anti-viral prophylaxis for HBV surface antigen (HBsAg) carriers starting anti-TNFα agents are not yet fully established, even in endemic regions of HBV infection. We retrospectively collected the clinical data of 52 HBsAg carriers with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) that had been administered anti-TNFα treatment at seven medical centers in South Korea. Periodic data of liver function tests and serum HBV DNA were both utilized to assess HBV reactivation. The YMDD motif mutation of HBV DNA polymerase was tested in lamivudine-treated patients with elevated HBV DNA. Three of the 52 patients were excluded from the analysis. Of the 49 analyzed patients, 20 patients received anti-viral prophylaxis (15 lamivudine, five entecavir) with anti-TNFα treatment. The remaining 29 patients were treated with anti-viral agents if needed at the discretion of the clinician and did not receive prophylaxis. Of the 29 patients who did not receive primary prophylaxis, two (6.9%) developed viral reactivation within a year of anti-TNFα treatment. In the prophylaxis group, one patient developed viral reactivation at week 64 of anti-TNFα therapy attributed to YMDD mutation caused by lamivudine. Patients with HBV reactivation all responded well to anti-viral therapy. In summary, anti-viral prophylaxis helped preventing HBV reactivation in HBsAg carriers with RA or AS starting anti-TNFα, yet mutation in the YMDD motif of HBV DNA polymerase could be detrimental to some patients under long-term lamivudine prophylaxis.

Background/Aims:A cross-sectional study was undertaken to investigate the association between severity of periodontitis and clinical manifestation of rheumatoid arthritis (RA).Methods:Two hundred sixty-four RA patients and 88 age- and sex-matched controls underwent dental exam. Additionally, clinical manifestations including disease activity and anti-citrullinated protein antibodies were evaluated in RA patients.Results:The prevalence of moderate or severe periodontitis was higher in RA patients compared to controls (63.6% vs 34.1%, p < 0.001). In markers of periodontal inflammation, bleeding on probing was correlated with disease activity score 28 (r = 0.128, p = 0.041), RA disease duration (r = 0.211, p = 0.001), erythrocyte sedimentation rate (ESR; r = 0.141, p = 0.023), anti-cyclic citrullinated peptide antibody (r = 0.183, p = 0.009), and anti-citrullinated α-enolase peptide-1 antibody (r = 0.143, p = 0.025). Gingival index was correlated with RA duration (r = 0.262, p < 0.001), ESR (r = 0.162, p = 0.009), anti-cyclic citrullinated peptide antibody (r = 0.203, p = 0.004) and anti-citrullinated α-enolase peptide-1 antibody (r = 0.225, p < 0.001). Periodontal structural damage represented by probing pocket depth and clinical attachment level were less in RA patients with human leukocyte antigen (HLA)-DRB1 shared epitope compared than those without shared epitope (p = 0.005 and p =0.006, respectively).Conclusions:The prevalence of moderate or severe periodontitis was increased in RA patients compared to controls. Periodontal inflammation was correlated with RA disease duration, ESR, and anti-citrullinated protein antibodies. Periodontal structural damage was less in RA patients with HLA-DRB1 shared epitope.

BackgroundPeriodontitis (PD) has been reported to be associated with rheumatoid arthritis (RA). Porphyromonas gingivalis (P. gingivalis) is a gram-negative anaerobic bacterium that is recognized as one of the major pathogenic organisms in PD and is the only bacterium known to express peptidylarginine deiminase (PAD). Antibody against human α-enolase (ENO1) is one of the autoantibodies in RA. ENO1 is a highly conserved protein, and could be a candidate molecule for molecular mimicry between bacterial and human proteins. In the present study, we measured serum antibody against P. gingivalis and human ENO1 in patients with RA and investigated their association with the severity of PD or disease activity of RA.MethodsTwo hundred, forty-eight patients with RA and 85 age- and sex-matched healthy controls were evaluated by rheumatologic and periodontal examinations. The serum levels of anti-P. gingivalis and anti-ENO1 antibodies were measured by an enzyme-linked immunosorbent assay (ELISA).ResultsPatients with RA had significantly higher levels of anti-P. gingivalis and anti-ENO1 antibody titers than the controls (p = 0.002 and 0.0001, respectively). Anti-P. gingivalis antibody titers significantly correlated with anti-ENO1 antibody titers in RA patients (r = 0.30, p < 0.0001). There were significant correlations between anti-P. gingivalis antibody titers and the gingival index (GI), probing pocket depth (PPD), bleeding on probing (BOP) and clinical attachment level (CAL) (p = 0.038, 0.004, 0.004 and 0.002, respectively) in RA. Anti-P. gingivalis antibody titers were not correlated with disease activity score 28 (DAS28) or anti-CCP titer. However, anti-ENO1 antibody titers were significantly correlated not only with the periodontal indices, such as PPD, BOP, and CAL (p = 0.013, 0.023 and 0.017, respectively), but also RA clinical characteristics, such as DAS28, anti-CCP titer, and ESR (p = 0.009, 0.015 and 0.001, respectively).ConclusionAnti-P. gingivalis and anti-ENO1 antibody titers were correlated with the severity of PD in RA. Anti-ENO1 antibody titers, but not anti-P. gingivalis antibody titers, were further associated with RA disease activity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-015-0647-6) contains supplementary material, which is available to authorized users.

Hydrogen sulfide (H2 S) is a potent vasodilator and regulates cardiovascular homeostasis. Furthermore, H2 S has a crucial role in ischemia-reperfusion injuries, especially of the heart, liver, and kidneys. This study indicates that treatment with hydrogen sulfide is able to restore neurological function after ischemic stroke by promoting angiogenesis. Treatment with H2 S augments angiogenesis in the peri-infarct area, and it significantly improves functional outcomes after 2 weeks in a rat MCAO model. H2 S promotes the phosphorylation of AKT and ERK and increases the expression of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1). H2 S-treated rats showed more newly synthesized endothelial cells in the ischemic lesion (2.31-fold, P < 0.01). H2 S-treated astrocytes increased VEGF and Ang-1 expression, and the inhibition of phosphatidylinositide 3-kinase (PI3K)/AKT signaling by LY294002 significantly reduced H2 S-induced VEGF and Ang-1 expression in astrocytes. Finally, H2 S stimulated endothelial cell migration (3.92-fold increase in wound healing assay) and tube formation (3.69-fold increase, P < 0.001) through PI3K/AKT signaling. In conclusion, treatment with H2 S promotes angiogenesis and thereby contributes to improvement of functional outcome after cerebral ischemia. Our findings strongly suggest that H2 S may be of value in regenerative recovery after stroke.