The level of serum Dkk-1 was correlated with a swollen joint count, and levels of complement components 3 and 4

The level of serum Dkk-1 was correlated with a swollen joint count, and levels of complement components 3 and 4. 3 and 4. Elevated Dkk-1 level (odds ratio?=?4.440, 95% confidence interval: 1.246C15.817, (percentage), mean??standard deviation, or median (P25, P75). Statistical significance between groups was assessed with values? ?0.050 were considered significant. The cut-off value of Dkk-1 concentrations was decided using a receiver operating characteristic (ROC) curve. Results Characteristics of study participants The major demographic, clinical and laboratory features, and radiographic evaluations are shown in Table ?Table1.1. Among NVP-BHG712 69 patients with PsA, 56.5% were female, the mean age was 52.7??13.0 years, mean arthritis and psoriasis duration were 5.0 (1.6, 13.0) and 12.0 (5.0, 20.0) years, and 17.4% (12/69) of them had a family history of skin psoriasis or PsA. Nail psoriasis, dactylitis, enthesitis, and uveitis were observed in 43.5%, 10.1%, 27.5%, and 2.9% of the PsA patients, respectively. NVP-BHG712 Positive RF (8.7% values(%)12 (17.4)NANACCTender joint count, 0C46, (%)6.0 (2.0, 12.5)8.0 (5.0, 12.0)NA?1.400?0.161Swollen joint count, 0C44, (%)3.0 (0, 8.0)4.0 (2.0, 7.0)NA?1.445?0.148Nail psoriasis, (%)30 (43.5)NANACCDactylitis, (%)7 (10.1)NANACCEnthesitis, (%)19 (27.5)NANACCUveitis, (%)2 (2.9)NANACCRF-positive, (%)6 (8.7)31 (79.5)NA55.440? 0.010Anti-CCP-positive, (%)4 (5.8)38 (97.4)NA87.130? 0.010HLA-B27-positive, (%)14 (20.3)NANACCSacroiliitis, (%)32 NVP-BHG712 (46.4)NANACCBone erosion, (%)26 (37.7)19 (48.7)NA1.249?0.264 Open in a separate window Age and disease duration are respectively presented as mean??SD and median (P25, P75). ?Differences were analyzed by one-way analysis of variance (ANOVA) with Holm-Sidak multiple comparisons test for three groups, the statistics value was Anti-CCP: Anti-cyclic citrullinated peptide; HCs: Healthy controls; HLA-B27: Human leukocyte antigen-B27; NA: Not assessed; Ps: Psoriasis; PsA: Psoriatic arthritis; RA: Rheumatoid arthritis; RF: Rheumatoid factor; SD: Standard deviation. Dkk-1 level was elevated in sera of patients with PsA As shown in Figure ?Physique1,1, Dkk-1 was elevated in 68.1% (47/69) of the patients with PsA, 46.2% (18/39) of RA patients, and 9.5% (2/21) of HCs. Serum Dkk-1 level in PsA patients (9.269??3.276 ng/mL) was significantly higher than that in patients with RA (7.862??2.487 ng/mL, valuesvalue(%)8 (17.0)4 (18.2)0?1.000Tender joint count, (%)6.0 (2.0, 13.8)6.0 (3.5, 10.8)?0.019?0.985Swollen joint count, (%)4.0 (1.0, 9.3)1.0 (0, 4.5)?2.103?0.035Nail psoriasis, (%)20 (42.6)10 (45.5)0.051?0.821Dactylitis, (%)6 (12.8)1 (4.5)0.392?0.531Enthesitis, (%)16 (34.0)3 (13.6)3.127?0.077Uveitis, (%)1 (2.1)1 (4.5)0?1.000WBC (109/L)6.62??1.757.73??4.21?1.199?0.242Hb (g/L)117.60??18.17121.58??15.17?0.892?0.376PLT (109/L)250.00 (180.00, 287.30)248.00 (198.25, 329.33)?0.579?0.562ESR (mm/h)46.00 (15.00, 74.00)40.50 (15.75, 88.00)?0.161?0.872CRP (mg/L)16.60 (5.01, 48.70)25.50 (8.09, 92.00)?1.275?0.202IgA (g/L)3.31 (2.14, 5.04)3.26 (2.25, 5.05)?0.262?0.793IgG (g/L)13.59??3.7017.29??9.39?1.781?0.087IgM (g/L)0.90 (0.71, 1.30)1.02 (0.89, 1.49)?1.265?0.206Complement C3 (g/L)1.11??0.341.29??0.26?2.133?0.037Complement C4 (g/L)0.25??0.090.26??0.08?0.548?0.586RF-positive, (%)3 (6.4)3 (13.6)0.290?0.590Anti-CCP-positive, (%)3 (6.4)1 (4.5)0?1.000HLA-B27-positive, (%)9 (19.1)5 (22.7)0.001?0.981Sharp score9.0 (0, 17.0)3.0 (0, 7.0)?2.067?0.039Sacroiliitis, (%)27 (57.4)5 (22.7)7.264? 0.010RAD, (%)30 (63.8)8 (36.4)4.569?0.033Bone erosion, (%)22 (46.8)4 (18.2)5.230?0.022 Open in a separate window ?Differences were analyzed by values /thead Univariate?Age0.9950.958C1.0330.786?Dkk-1 elevated3.9601.163C13.4880.028?Duration of arthritis1.0030.965C1.0430.871?Duration of psoriasis1.0280.984C1.0740.222?Tender joint count1.0170.969C1.0670.490?Swollen joint count1.0340.955C1.1190.414?Nail psoriasis2.5450.937C6.9140.067?Dactylitis4.8810.872C27.3150.071?Enthesitis1.7470.597C5.1130.309?Uveitis1.6800.101C28.0640.718Multivariate?Dkk-1 elevated4.4401.246C15.8170.021 Open in a separate window CI: Confidence intervals; Dkk-1: Dickkopf-1; OR: Odds ratio; PsA: Psoriatic arthritis. Discussion In this study, we exhibited that serum Dkk-1 was significantly elevated in PsA patients compared with RA patients and HCs, supporting the idea that Dkk-1 might be involved in the pathogenesis of PsA. A key obtaining of our study is that increased Dkk-1 was correlated with bone erosion in PsA patients. PsA is usually a chronic autoimmune disorder that attacks enthesis and synovial joints, resulting in bone destruction. Progressive bone erosion and new bone formation are hallmarks of PsA, so finding SH3BP1 the main molecules involved in bone erosion is essential for determining the mechanism of PsA. Dkk-1 is usually a key inhibitor in Wnt signaling by binding to the Wnt co-receptor low density lipoprotein receptor-related protein 5/6 (LRP5/6).[18,19] Wnt signaling via LRP5 impacts accrual and is crucial for peak bone mass establishment.[20] The LPR5 mutation causes high bone density, by reducing the action of a normal antagonist of the Wnt-mediated pathway and thus promoting Wnt signaling.[21] These findings indicate that Dkk-1 is a potential treatment or prevention target of osteoporosis or bone erosion.[8,20C22] Dkk-1 functions directly in the differential remodeling of human joint architecture by diverse mechanisms. For example, an elevated level of Dkk-1 impairs bone formation by upregulating the expression of inflammatory cytokines including tumor necrosis factor (TNF).[23,24] Additionally, lower Dkk-1 contributes to the appearance of osteophytes.[24] PsA is a heterogeneous disease that may manifest both patterns of osteopathology, either bone loss or bone remodeling.[3,4,16] The mechanism of PsA joint remodeling is unknown.