Background Immune and non-immune cells contribute to the pathology of chronic arthritis and they can contribute to tissue remodeling and repair as well as disease pathogenesis. An important role for their products such as TGF-beta 1, IL17 or BMPs has been suggested in homeostatic and remodeling mechanisms in arthritis. BMP signaling could have an anti-inflammatory role in the control and maintenance of low levels of pro-inflammatory factors in healthy joints or the early stage of RA.
Objectives to analyze and compare serum levels, gene expression and immunohistochemistry (IHC) in synovial membrane of inflammation and bone destruction/regeneration biomarkers in patients with psoriatic arthritis (PsA), undetermined seronegative arthritis (USA), Osteoarthritis of the knee (kOA) and ankylosing spondylitis (AS).
Methods We recruited 45 consecutive patients with chronic knee arthritis referred for undergoing arthroscopies (17 PsA, 12 USA, 12 kOA, 4 AS). Synovial membrane was processed for IHC analysis and quantification of mRNA expression ratio by qRT-PCR. Serum levels of TGF-beta 1, IL6, IL17 and IL22, DKK1, Sclerostin, BMP2, BMP4, Wnt1 and Wnt5a were measured (ELISA). We analyzed and compared these data with the demographic, clinical, analytical and radiological characteristics of the patients. Data were analyzed using the SPSS version 17.0 software and statistical significance was defined as P<0.05.
Results We obtained valid synovial membrane samples from 41 patients for IHC, RNA extraction and purification from 29 patients for analyze mRNA expression and serum from 38 patients for protein levels measurement. IL17 gene expression was higher in PsA patients (p=0.027) and correlated positively with DKK1 (r=0.424, p=0.022) and negatively with BMP2 (r=-0.396, p=0.033) and BMP4 (r=-0.472, p=0.010). IHC reactivity for TGF-beta 1 in synovial tissue was higher in patients with psoriatic arthritis (p 0.010) and correlated positively with IL17 (r=0.389, p=0.012) and DKK1 (r=0.388, p=0.012). Moreover, serum levels of TGF-beta 1 were significantly increased in PsA with erosions (p=0.044).
Conclusions IL17 gene expression in synovial membrane from patients with psoriatic arthritis was higher than in seronegative undetermined arthritis, osteoarthritis and ankylosing spondylitis patients, correlating positively with DKK1 and negatively with bone morphogenetic proteins 2 and 4. In addition, TGF-beta in synovial tissue, necessary for the activation of Th17 cells, was higher in patients with psoriatic arthritis, in relation to IL17 and DKK1 increased. Serum TGF beta 1 levels were also higher in patients with erosive disease.
Varas A, Valencia J, Lavocat F, Martínez VG, Thiam NN, Hidalgo L, et al. Blockade of bone morphogenetic protein signaling potentiates the pro-inflammatory phenotype induced by interleukin-17 and tumor necrosis factor-α combination in rheumatoid synoviocytes. Arthritis Res Ther. 2015;17:192. doi: 10.1186/s13075–015–0710–6.
Acknowledgements This work has been supported by grant PI11/00390 from Plan Nacional de Investigaciόn Científica, Desarrollo e Innovaciόn Tecnolόgica 2008–2011 y cofinanciado por el ISCIII-Subdirecciόn General de Evaluaciόn y Fomento de la Investigaciόn - Fondo Europeo de Desarrollo Regional (FEDER).
Disclosure of Interest None declared