Association between leukocyte telomere length and angiogenic cytokines in knee osteoarthritis.

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 ± 0.4 vs. 1.3 ± 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 = -0.377, P = 0.017), VEGF (r = -0.405, P = 0.009) and G-CSF (r = -0.347, 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.

Association between ADAM12 polymorphism and knee osteoarthritis in Thai population.

BACKGROUND: Osteoarthritis (OA), a common degenerative joint disorder in the elderly, is characterized by the destruction of articular cartilage, bony outgrowths at joint margins, and synovitis. The objective of this study was to evaluate whether there is an association between the ADAM12 (rs3740199) polymorphism and susceptibility to knee OA in a Thai population. METHODS: Genomic deoxyribonucleic acid (DNA) was isolated from 200 Thai knee OA patients and 200 healthy controls. High resolution melting analysis was used to detect ADAM12 polymorphisms. The melt profile of all DNA samples was generated on the CFX96™ real-time polymerase chain reaction system and analyzed by Precision Melt Analysis™ software. The genotype distributions and allele frequencies of ADAM12 were compared between groups using the StatCalc program. RESULTS: The significant associations were shown from the C allele (OR=2.10, 95% CI=1.16-3.79, P=0.008) and the CC genotype (OR=4.28, 95% CI=1.21-15.72, P=0.01) in male knee OA patients. No significant association was observed in female patients. CONCLUSION: The rs3740199 in ADAM12 was associated with knee OA susceptibility in Thai male patients, and individuals with the CC genotype carried the highest risk when compared with the GG and GC genotypes. CLINICAL RELEVANCE: The rs3740199 polymorphism of the ADAM12 gene can potentially be used to determine genetically high-risk subgroup of knee osteoarthritis and to better understand the pathogenesis of knee osteoarthritis.

Adipokines: Biomarkers for osteoarthritis?

Osteoarthritis (OA) is one of the most common degenerative joint diseases in aging population. Obesity is an important risk factor for initiation and progression of OA. It is accepted that excess body weight may lead to cartilage degeneration by increasing the mechanical forces across weight-bearing joints. However, emerging data suggest that additional metabolic factors released mainly by white adipose tissue may also be responsible for the high prevalence of OA among obese people. Adipocyte-derived molecules ''adipokines'' have prompt much interest in OA pathophysiological research over the past decade since they play an important role in cartilage and bone homeostasis. Therefore, the aim of this review is to summarize the current knowledge on the role of adipokines including leptin, adiponectin, visfatin and resistin in OA and their potential to be used as biomarkers for earlier diagnosis, classifying disease severity, monitoring disease progression, and testing pharmacological interventions for OA. In OA patients, leptin, visfatin and resistin showed increased production whereas adiponectin showed decreased production. Leptin and adiponectin are far more studied than visfatin and resistin. Importantly, altered adipokine levels also contribute to a wide range of diseases. Further experiments are still crucial for understanding the relationship between adipokines and OA.