Abstract
BackgroundOxidative stress due to the overproduction of nitric oxide (NO) and other oxygen reactive species (ROS), play a main role in the initiation and progression of the OA disease and leads to the degeneration of mitochondria. Therefore, the goal of this work is to describe the difference in telomere length of peripheral blood leukocytes (PBLs) and Nitric Oxide (NO) production between mitochondrial DNA (mtDNA) haplogroup J and non-J carriers, as indirect approaches of oxidative stress.MethodsThe telomere length of PBL was analyzed in DNA samples from 166 healthy controls (114 J and 52 non-J) and 79 OA patients (41 J and 38 non-J) by means of a validated qPCR method. The NO production was assessed in 7 carriers of the haplogroup J and 27 non-J carriers, by means of the colorimetric reaction of the Griess reagent in supernatants of cultured chondrocytes. Inducible nitric oxide synthase (iNOS) mRNA from these samples was analyzed by qPCR. Appropiated statistical analyses were performedResultsCarriers of the haplogroup J showed a significantly longer telomere length of PBLs than non-J carriers, regardless of age, gender and diagnosis (p = 0.025). Cultured chondrocytes carrying the mtDNA haplogroup J also showed a lower NO production than non-J carriers (p = 0.043). No significant correlations between age and telomore length of PBLs were detected neither for carriers of the haplogroup J nor for non-J carriers. A strong positive correlation between NO production and iNOS expression was also observed (correlation coefficient = 0.791, p < 0.001).ConclusionThe protective effect of the mtDNA haplogroup J in the OA disease arise from a lower oxidative stress in carriers of this haplogroup, since this haplogroup is related to lower NO production and hence longer telomere length of PBLs too.
Highlights
Oxidative stress due to the overproduction of nitric oxide (NO) and other oxygen reactive species (ROS), play a main role in the initiation and progression of the OA disease and leads to the degeneration of mitochondria
Telomere length The non-parametric analysis of the telomere length of peripheral blood leukocytes (PBL) between OA patients and healthy controls showed that OA patients had a shorter telomere length than healthy controls (0.986 vs 1.008 respectively), this difference did not reach the statistical significance between both groups (Table 1)
The rest of variables tested such as age, gender and diagnosis did not show any influence on the telomere length of PBLs
Summary
Oxidative stress due to the overproduction of nitric oxide (NO) and other oxygen reactive species (ROS), play a main role in the initiation and progression of the OA disease and leads to the degeneration of mitochondria. Osteoarthritis (OA), the most common form of joint disease and cause of musculoskeletal disability in elderly people, is a disease affecting articular cartilage, bone and soft tissue leading to joint destruction and severe impairment of mobility [1] It is the main cause of work incapacity and one of the most common reasons for visiting primary physicians. The increased levels of these ROS have been correlated to increased levels of inflammatory cytokines, such as interleukin-1 (IL-1), which is implicated in the degeneration of cartilage due to its induction of proteoglycan loss and matrix degradation [4] Both IL-1 and mechanical loading of cartilage increase the production of NO by upregulating the nitric oxide synthase 2 [5]; and most of the destructive effects of NO in articular cartilage are related to the ability of NO to combine with superoxide anions (O2-) to generate peroxynitrite (ONOO-) [6,7]. This latter aspect would strengthen the role of the mitochondria in the OA disease, as previously described [6,12,13,14,15]
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