Effects of formononetin on inflammatory response,cartilage damage and T helper cell 17/interleu-kin-26 inflammatory axis in rats with osteoarthritis
Objective To explore the effects of formononetin(FMN)on inflammatory response,cartilage damage and T helper cell 17(Th17)/interleukin(IL)-26 inflammatory axis in rats with osteoar-thritis(OA).Methods A total of 60 healthy male SD rats without specific pathogen level provided by Nanjing Jicui Yaokang Company were divided into four groups according to the random number table meth-od,with 15 rats in each group.The rats in the control group only opened the joints without other operations to implement sham operation.The rats in OA+FMN group and OA+FMN+ABBV-157 group were injec-ted with FMN(10 mg/kg)through the tail vein once a day for 4 weeks.In the OA+FMN+ABBV-157 group,the Th17 differentiation function was promoted by peritoneal injection of accutane associated orphan receptor γt antibody(RORγt)agonist ABBV-157(5 mg/kg)twice a week for 4 weeks.The other groups were injected with the same amount of normal saline.Joint inflammation,cartilage degeneration,Th17 cell ratio and ROR gamma T protein(RORγt)and IL-26 protein levels were detected.All data were analyzed using independent sample t-tests,one-way ANOVA,SNK-q tests,and other statistical methods.Results The osteoarthritis research society international(OARSI)scores of the OA group,OA+FMN group,and OA+FMN+ABBV-157 group were higher than those of the control group(4.23±0.56,1.98±0.25,4.11±0.60 vs.1.08±0.14,t=21.135,12.165,17.374,P＜0.05),and the OARSI score of the OA+FMN group was significantly lower than that of the OA group and OA+FMN+ABBV-157 group(t=14.209,12.691,P＜0.05).The levels of IL-1β[(23.82±1.98),(11.37±1.06),(23.14± 2.24)μg/ml vs.(6.56±0.75)μg/ml]and IL-6[(30.38±3.12),(13.77±1.45),(29.52± 2.80)μg/ml vs.(8.54±0.95)μg/ml]in the OA group,OA+FMN group,and OA+FMN+ABBV-157 group were higher than those in the control group(t=31.572,14.307,27.184,25.935,11.685,27.481,P＜0.05),and the levels of IL-1 β and IL-6 in the OA+FMN group were lower than those in the OA group and OA+FMN+ABBV-157 group(t=21.470,18.395,18.698,19.345,P＜0.05).The Th17 level in the OA group,OA+FMN group,and OA+FMN+ABBV-157 group[(21.00±1.65)％,(10.21±1.06)％,(21.63±2.29)％vs.(3.96±0.52％)]was higher than that in the control group(t=38.148,20.502,29.143,P＜0.05),while the Th17 level in the OA+FMN group was lower than that in the OA group and OA+FMN+ABBV-157 group(t=38.148,17.528,P＜0.05).The RORγt(0.54±0.05,0.26±0.03,0.55±0.06 vs.0.13±0.02)and IL-26(0.60±0.06,0.27±0.03,0.58±0.06 vs.0.11±0.02)levels in the OA group,OA+FMN group,and OA+FMN+ABBV-157 group were higher than those in the control group(t=29.487,13.964,25.720,30.006,17.187,28.782,P＜0.05).The RORγt and IL-26 levels in the OA+FMN group were lower than those in the OA group and OA+FMN+ABBV-157 group(t=18.598,16.763,19.053,17.898,P＜0.05).Conclusion FMN alleviates inflammatory response and cartilage damage in OA rats by inhibiting Th17/IL-26 inflammatory axis.
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