Progranulin (PGRN) is a growth factor that has antiinflammatory, immunosuppressive, and chondroprotective effects. It blocks Tumor Necrosis Factor-α (TNF-α) signal pathway by binding its receptor. Recently, it has been claimed that PGRN may be overexpressed in patients with Osteoarthritis (OA). However, these patients tend to be obese and obesity also may be one of the factors that affect PGRN levels. The aim of this study was to compare the PGRN levels of patients with Knee OA (KOA) with that of healthy controls by eliminating the effect of obesity and to evaluate PGRN-to-Tumor Necrosis Factor-α (TNF-α) ratio in KOA, both of which were investigated first in literature by this study.
A total of 80 individuals (40 patients with KOA and 40 healthy controls) were included in this study. The patients and controls were divided into two groups according to their Body Mass Indexes (BMI): nonobese (BMI between 18.5 and 24.9) and obese (BMI of 30 or higher). Each of the groups included 20 subjects and had an equal number of men and women. Blood samples were obtained from all participants, and the serum PGRN and TNF-α levels were measured using commercial ELISA kits.
There was no difference among groups in terms of age (P = 0.416) and gender distribution. There was no statistical difference among study groups with regard to serum PGRN levels. Serum TNF-α levels were significantly higher in obese controls (P < 0.001) and nonobese patients (P = 0.003) compared to that of nonobese healthy controls. Correspondingly, serum PGRN-to-TNF-α ratio was considerably lower in obese controls (P < 0.001) and nonobese patients (P < 0.001) by comparison with that of nonobese healthy controls.
Level III, Diagnostic study.
We determined that both obesity and KOA increased serum TNF-α levels and concordantly decreased serum PGRNto- TNF-α ratio. The results of the study suggest that the activation of the PGRN pathway and/or the inhibition of the TNFα pathway may be essential in terms of the reestablishment of the disrupted inflammatory balance in patients with KOA.