Association between leukocyte telomere length and angiogenic cytokines in knee osteoarthritis

Abstract

Aim: The aims of this study were to compare leukocyte relative telomere length (RTL) in knee osteoarthritis (OA) patients and healthy controls and to investigate associations between plasma angiogenic cytokine concentrations and leukocyte RTL.Method: Eighty knee OA patients and 60 age-matched controls were enrolled. Leukocyte RTL was assessed using real-time quantitative polymerase chain reaction (qPCR). Angiogenic cytokines were measured by a multiplex immunoassay.Results: Leukocyte RTL in knee OA patients was significantly lower than that in healthy controls (1.1 AE 0.4 vs. 1.3 AE 0.6, P = 0.039). Plasma angiopoietin-2, follistatin, granulocyte-colony stimulating factor (G-CSF), hepatocyte growth factor (HGF), interleukin-8 (IL-8), platelet endothelial cell adhesion molecule-1 (PECAM-1), and vascular endothelial growth factor (VEGF) levels in knee OA patients were higher than those in controls (P < 0.01). Correlation analysis revealed significant negative correlations between leukocyte RTL and plasma levels of HGF (r = À0.377, P = 0.017), VEGF (r = À0.405, P = 0.009) and G-CSF (r = À0.347, P = 0.026). In contrast, plasma angiopoietin-2, follistatin, IL-8, leptin, platelet-derived growth factor-BB and PECAM-1 were not correlated with leukocyte RTL. Conclusion:Telomere length was shortened in knee OA patients compared to healthy controls. Plasma HGF, VEGF and G-CSF were negatively correlated with leukocyte RTL, suggesting involvement of telomere shortening and these cytokines in knee OA.

Telomere length and telomerase activity in osteoporosis and osteoarthritis (Review)

“…Notably, plasma hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and granulocyte-colony stimulating factor (G-CSF) levels were found to be negatively associated with leukocyte RTL. Therefore, that study indicated that high circulating angiogenic cytokine levels in the knees of patients with OA may reflect high oxidative stress and chronic inflammation, leading to subsequent telomere shortening (58). Indeed, overall oxidative stress can expedite telomere shortening either indirectly through increase in cell division, or directly acting on DNA telomere repeats, suggesting that redox balance is a prominent factor that regulates chondrocytes lifespan (59).…”

The future of telomere length in personalized medicine

“…VEGF positively regulates telomerase activity in both in vivo and in vitro models (87,88). However, some epidemiological studies have shown that plasma VEGF is negatively or not correlated with TL (76,89). In addition, hepatocyte growth factor and granulocyte colony-stimulating factor, which contribute significantly both in physiological and pathological angiogenesis, were also found to be negatively correlated with TL in knee osteoarthritis patients (Table 1) (89).…”

“…However, most of the studies linking TL to inflammatory biomarkers were based on crosssectional design, and therefore, cannot explain the bi-directionality that exists between TL shortening and inflammation. It is, therefore, highly desirable to use data from longitudinal studies with large sample sizes in order to determine the evolution of various biomarkers at multiple time points, which will allow to better explore the telomere dynamics in relation with various chronic diseases (76,89,102,103).…”

Predictors of Osteoarthritis Pain: the Importance of Resilience

“…In the context of OA, shorter telomere length was found in knee osteoarthritis patients with high levels of stress and pain [20], with a later study by the same authors largely confirming these results by observing shorter telomeres among individuals with the greatest burden of chronic knee pain [21]. Interestingly, a recent investigation demonstrated an association between angiogenic cytokines (i.e., hepatic growth factor, vascular endothelial growth factor, granulocyte-colony stimulating factor) and telomere length in knee OA, suggesting a potential role for these factors in cellular aging and OA pathogenesis [22]. …”