Molecular phenotypes of osteoarthritis

Abstract

Purpose: To evaluate the clinical and pathogenetic relationships of inflammatory, oxidative and mixed molecular subtypes of osteoarthritis (OA). Methods: 65 patients with osteoarthritis (OA) of knee joints were examined at 6.7±7.9 years, the duration of the disease was 1 to 18 years (5.9±4.0 years). For molecular phenotyping, plasma concentrations of IL-1β and OSGIN-1 were determined. phenotypes OA: inflammatory, oxidative and mixed. To determine the molecular phenotypes of OA, the "classification trees" method was applied. Serum concentrations of IL-1β and OSGIN-1 were used as predictor variables. As a classification response, increased values of the level of molecules above the 99th percentile of the reference interval are determined. In addition, plasma ELISA: CRTAP (cartilage-associated protein), GDF-5 (growth and differentiation factor 5), FAS (factor apoptosis-related), OSGIN-1 (oxidative stress-inducing inhibitor of growth 1), IL -1β (interleukin-1 beta). Results: Inflammatory phenotypes occurred in 13.8% (n=9) cases, oxidative (n=28) and mixed (n=28) in 43.1% of observations. The pain level measured by the VAS was the lowest in patients with the inflammatory molecular subtype as compared to the groups of oxidative and mixed phenotypes (p=0.006). The total score of WOMAC was significantly higher in patients with mixed endotypes compared with inflammatory and oxidative (p=0.03). The concentration of CRTAP was significantly lower in patients with inflammatory and oxidative molecular phenotypes compared with the mixed phenotype (p=0.03). The level of the FAS ligand was significantly lower in the group of patients with an inflammatory molecular subtype of OA compared to the oxidative and mixed subtypes (p=0.03). The level of endothelin-1 was significantly lower in patients with oxidative endothelium compared with inflammatory (p=0.04). The concentration of GDF-5 was significantly higher in the inflammatory phenotype group than in the mixed and oxidative molecular endotypes of OA (p=0.02). In the group of patients with inflammatory phenotypes, the pain level directly correlated with the concentration of GDF-5 and CRTAP (respectively: r=0.8; r=0.7). In patients with oxidative molecular subtypes of OA, the pain and functional level had an inverse relationship with the concentration of GDF-5 (r = -0.7, r = -0.8) and FAS (respectively: r=-0.5; r=-0.4). In patients with OA with an oxidative subtype of OA, pain had a direct correlation with GDF-5 and FAS (respectively: r=0.5; r=0.4). The X-ray stage of OA in this group had a negative relationship with the concentration of the FAS ligand (r=-0.4). Conclusions: Discrimination of patients with OA on molecular basis can be considered as a promising method from a clinical and pathogenetic point of view.In this study, three types of systemic molecular responses to stress were studied: inflammatory, oxidative and mixed. Inflammatory molecular phenotypes are characterized by a relatively rare frequency of occurrence, low levels of structural and clinical manifestations of the disease. At the heart of this subtype lies the phenotypes model, realized through growth and differentiation factors. With the oxidative endotype, there is a "classical" scenario of free radical oxidation, manifested in the clinical and structural originality of OA. Mixed phenotype is characterized by severe radiographic and algofunctional manifestations of OA. The severe course of the disease is due to the implementation of the pathogenetic model of synergism of inflammation and oxidative stress. Thus, the data obtained by us on the clinical and pathogenetic features of different molecular endotypes of osteoarthritis can be used as a basis for a personified approach when choosing approaches to the treatment of patients with OA and require further study in large cohorts of the examined.