COMORBIDITY, DNA METHYLATION AND AUTOIMMUNITY IN DIABETES-ASSOCIATED OSTEOARTHRITIS: AN EXPLORATORY STUDY

Abstract

Osteoarthritis (OA) is among challenging problems of clinical medicine, not only due to its high prevalence, but also because of higher burden of comorbidities. Previously we described a clinical phenotype of OA associated with type 2 diabetes mellitus (OADM), which is one of OA phenotypes characterized by increased severity and reduced quality of life. In current literature, there is a lack of data on OADM biomarkers. Based on the current knowledge on type 2 DM and OA pathogenesis, it may be suggested that disturbances of DNA methylation may present the key pathogenetic mechanism for the both diseases. A number of factors, for example, chronic systemic inflammation, or increased levels of advanced glycation end products, may lead to increased articular cartilage degradation in type 2 DM-associated OA. Both OA and type 2 DM are characterized by higher comorbidity burden, thus allowing to suggest that coexistence of these diseases leads to additive effects upon comorbidity indices. In this exploratory study, we evaluated levels of total DNA methylation in peripheral blood mononuclear cells (PBMC), along with biomarkers of serum cartilage degradation and comorbidity features in patients with OA associated with diabetes (OADM). Global DNA methylation in PBMC was assessed as 5-methylcytosine levels using flow cytometry. Circulating aggrecan and anti-CII antibody concentrations were measured by means of ELISA. Comorbidity indices were assessed using Cummulative Illness Rating Scale (CIRS-G). A total of 78 patients with generalized OA were assessed. Fifty two patients had clinical manifestations of OA preceded by DM type II for 1 year (case group), and 26 OA patients were non-diabetic (control group). Patients with OADM had more pronounced joint impairment and higher severity of comorbidity. There were no differences in other measures of comorbidity between the compared groups. In conclusion, further studies on epigenetic control of inflammation and cartilage metabolism in patients with OA will enable to identify new therapeutic targets and to define new treatment strategies for the both basic disorder and comorbidity states.

Keywords

• osteoarthritis
• diabetes mellitus
• dna methylation
• immune system