Abstract
Endocrine disorders have become more and more frequently diagnosed in humans and animals. In horses, equine metabolic syndrome (EMS) is characterized by insulin resistance, hyperleptinemia, hyperinsulinemia, inflammation and usually by pathological obesity. Due to an increased inflammatory response in the adipose tissue, cytophysiological properties of adipose derived stem cells (ASC) have been impaired, which strongly limits their therapeutic potential. Excessive accumulation of reactive oxygen species, mitochondria deterioration and accelerated ageing of those cells affect their multipotency and restrict the effectiveness of the differentiation process. In the present study, we have treated ASC isolated from EMS individuals with a combination of 5‐azacytydine (AZA) and resveratrol (RES) in order to reverse their aged phenotype and enhance osteogenic differentiation. Using SEM and confocal microscope, cell morphology, matrix mineralization and mitochondrial dynamics were assessed. Furthermore, we investigated the expression of osteogenic‐related genes with RT‐PCR. We also investigated the role of autophagy during differentiation and silenced PARKIN expression with siRNA. Obtained results indicated that AZA/RES significantly enhanced early osteogenesis of ASC derived from EMS animals. Increased matrix mineralization, RUNX‐2, collagen type I and osteopontin levels were noted. Furthermore, we proved that AZA/RES exerts its beneficial effects by modulating autophagy and mitochondrial dynamics through PARKIN and RUNX‐2 activity.
Highlights
RUNX 2 mRNA was down-regulated in ASCs isolated from EMS horses (ASCEMS) in comparison to the control group (Figure 3B, P < .01); AZA/RES treatment significantly enhanced its expression (P < .001)
We found decreased synthesis of IL-10 in ASCEMS (Figure 3G, P < .001); its production was significantly increased in AZA/RES group (P < .001)
LAMP-2 expression was up-regulated in ASCEMS in comparison to ASCCTRL; no differences were found between ASCEMS and ASCEMS AZA/RES
Summary
Metabolic syndrome in both humans (MetS) and horses (EMS) is characterized by a set of interrelated physiological, biochemical, clinical and metabolic factors, including insulin resistance (IR), abnormalPrecise: In this work, we discovered that AZA/RES treatment enhances osteogenic differentiation of ASC isolated from EMS horses by modulation of mitochondrial dynamics.glucose tolerance, hyperleptinemia and obesity.[1,2] recent data excluded obesity in horses as a sine qua non diagnostic factor.[3,4] Adipose tissue in both species is recognized as an active endocrine organ, responsible for the synthesis and secretion of several hormones controlling nutritional intake (leptin, angiotensin), insulin sensitivity and inflammatory mediators, eg tumour necrosis factor a (TNF-a), resistin, visfatin, adiponectin and others.[5]. Microenvironment, combined with OS and inflammation in adipose tissues of EMS horses, is recognized as one of the most important factors that contributes to accelerated senescence and ageing.[1] Both inflammation and progressive ageing of adipose tissue are not without significance for adipose derived stem cells (ASCs) that reside within this tissue
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