Role Of Th17 Cells And Related Cytokines In The Pathogenesis Of Osteoporosis

Objective:Investigate of T helper cells 17(Th17),interleukin-17(IL-17),interleukin-23(IL-23),interleukin-6(IL-6)and receptor activator of nuclear factor kappa B ligand(RANKL)may play a role in the pathogenesis of osteoporosis(OP).This study analyzes the correlation between Th17 cells,cytokines IL-17,IL-23,IL-6,RANKL and bone mineral density in patients with osteoporosis,the correlation between Th17 cell ratio and IL-17,IL-23,IL-6,RANKL in patients with osteoporosis.All above are in order to provide new metod to further explore the pathogenesis of osteoporosis,and provide a new method for the prevention and treatment of osteoporosis in clinic.Methods:52 patients with osteoporosis were selected from December 2014 to March 2016 in Spine Department of Tianjin People’s Hospital during hospitalization with osteoporosis diagnostic criteria as osteoporosis group(OP group),there are 32 cases of female,20 cases of males among this group,aged 55-79 years old,the average age(69.1±8.6)years old.56 patients with normal bone mineral density and inclusion criteria were selected at the same time in the outpatient clinic of Tianjin People’s Hospital as control group(HC group),there are 34 cases of female,22 cases of males among this group,aged 53-74 years old,the average age(67.9±8.9)years old.There was no statistical difference in age,body mass index,sex ratio among all the subjects.The clinical data,BMD,laboratory examination of OP group were compared with those of HC group.Flow cytometry(FCM)were used to detect the percentage of Th17 cells in OP group and HC group’s fasting peripheral blood.The expression level of IL-17,IL-23,IL-6,RANKL in OP group and HC group’s fasting serum were determined by enzyme-linked immunosorbent assay(ELISA).The correlation was further analyzed between Th17,IL-17,IL-23,IL-6,RANKL and the bone mineral density in the peripheral blood of patients with osteoporosis.The correlation between the proportion of Th17 cells and the expression levels of IL-17,IL-23,IL-6,RANKL were analyzed in the OP group.Meanwhile the correlation between cytokines IL-17,IL-23,IL-6,RANKL in OP group were analyzed.Results:(1)In the fasting peripheral blood,the proportion of Th17 cells in the OP group was(2.77±0.93)%,the proportion of Th17 cells in the HC group was(1.32±0.42)%,the difference was statistically significant between the OP group and HC group(P<0.05).(2)The expression level of cytokines in the serum of OP group:IL-17(145.89±44.23pg/ml),IL-23(33.98±12.33pg/ml),IL-6(84.98±45.98pg/ml),RANKL(0.16±0.05μg/L),respectively;in the serum of HC group:IL-17(108.99±32.83pg/ml),IL-23(16.55±6.78pg/ml),IL-6(23.98±9.88pg/ml),RANKL(0.12±0.04μg/L),respectivel-y.the difference expression level of cytokines IL-17,IL-23,IL-6 and RANKL were statistically significant between the OP group and HC group(P<0.05).(3)the findings of Spearman correlation analysis:Ⅰ.OP group were found: the percentage of Th17 cells and bone mineral density were positively correlated(r=0.461,P=0.042),the cytokine RANKL expression level and bone mineral density were positively correlated(r= 0.552,P=0.032).Ⅱ.the percentage of Th17 cells and it’s related cytokines IL-17,IL-23,IL-6,RANKL expression levels were positively correlated in OP group(r=0.362,0.347,0.122,0.875,respectively;P=0.032,0.031,0.049,0.032,respectively).Ⅲ.the expression level of IL-17 and the expression level of IL-6,RANKL were positively correlated in OP group(r=0.353,0.435,respectively;P= 0.0 41,0.043,respectively).Conclusions:1.The proportion of Th17 cells and the expression levels of cytokines IL-17,IL-23,IL-6,RANKL in peripheral blood of patients with osteoporosis were increased,and the proportion of Th17 cells and the expression levels of RANKL were positively correlated with bone mineral density.2.The proportion of Th17 cells were positively correlated with the expression levels of IL-17,IL-23,IL-6,RANKL in peripheral blood of patients with osteoporosis,the expression levels of IL-17 were positively correlated with the expression levels of IL-6,RANKL in peripheral blood of patients with osteoporosis.3.Th17 cells and it’s related cytokines IL-17,IL-23,IL-6,RANKL expression were increased in peripheral blood of patients with osteoporosis,these results suggest that Th17 cells,IL-17,IL-23,IL-6,RANKL play an important role in the pathogenesis of osteoporosis,but further research is required in the specific mechanism of regulation of gene transcription.The proportion of Th17 cells and the expression levels of IL-17,IL-23,IL-6,RANKL in the peripheral blood may be used to diagnose osteoporosis and evaluate the therapeutic effect of osteoporosis.