Regulative Effects Of Salidroside On Wnt/β- Catenin Signaling Pathway In HFLS-RA Induced By TNF-αand Its Significance

Rheumatoid arthritis(RA)is a common autoimmune disease that is characterized by chronic,progressive,symmetrical and erosive destruction of peripheral joints.The basic pathological changes of RA is synovitis,excessive hyperplasia of fibroblast-like synoviocytes(FLS),a large number of T-lympho-cytes and macrophages infiltration and pannus formation.Paraplastic FLS secreting matrix metalloproteinases and inflammatory cytokines,triggering inflammation and immune response,is the main factor leading to cartilage and bone destruction,so it is the important strategy for the treatment of RA to inhibit hyperplasia of FLS or induce differentiation of FLS.Rhodiola is one of the traditional Chinese medicines to treat for RA.Salidroside is the most important active ingredient in Rhodiola,possesses multiple pharmacological properties including anti-oxidative,antifatigue,and anti-inflammatory,immunoregulation effects.This study proposed to take the FLS as the breakthrough point,Wnt/β-catenin signaling pathway as centre,and applied HFLS-RA cultured in vitro as the research object,to explore the mechanisms of Rhodiola to treat for RA.Objective:To investigate Salidroside’s regulation effect on β-catenin,MMP-7 and Cyclin-D1,to except to clarify pharmacological effect and mechanism of Salidroside to treat for RA,and provide basis for the application and development of Rhodiola.Methods:1.HLFS-RA were recovered and subcultured.2.HFLS-RA proliferation were observed by Methyl Thiazolyl Tetrazolium(MTT)mehthod.3.The expression of β-catenin,Cyclin-D1 and MMP-7 in supernatant fluid were measured by ELISA.4.The expression of β-catenin protein was detected by western blot.Results:1.Compared with NC group,The HFLS-RA proliferation in MC group were significantly increased(P<0.05);compared with MC group,the cell proliferation in 12.5μM and 25μM Salgroups were decreased but there were no significant differences(P>0.05),the cell proliferation in 50μM and 100μM Sal groups were significantly decreased(P<0.05),but there were no significant differences between the both groups(P>0.05)2.Compared with NC group,the expression of β-catenin,MMP-7 and Cyclin-D1 in supernatant fluid of the cell in MC group were increased respectively(P<0.05);compared with MC group,β-catenin,MMP-7 and Cyclin-D1 in 12.5μM and 25μM Sal groups were decreased,but there were no significant differences(P>0.05),β-catenin,MMP-7 and Cyclin-D1 in 50μM and 100μM Sal groups were decreased respectively(P<0.05),but there were no significant differences between the both groups(P>0.05).3.Compared with NC group,the expression of β-catenin in MC group were increased respectively(P<0.01);compared with MC group,the expression of β-catenin in 12.5μM and25μM Sal groups were decreased,but there were no significant differences(P>0.05),compared with MC group,the expression of β-catenin in 50μM and 100μM Sal groups were decreased respectively(P<0.05),but there were no significant differences between the both groups(P>0.05).Conclusions:1.TNF-α could promote the HFLS-RA proliferation,50μM and 100μM Sal could inhibit the proliferation of HFLS-RA induced by TNF-α.2.TNF-α could promote the secretion of β-catenin、MMP-7 and Cyclin-D1,50μM and100μM Sal could inhibit the secretion of β-catenin,MMP-7 and Cyclin-D1 in HFLS-RA induced by TNF-α.3.TNF-α could upregulate the secretion of β-catenin,50μM and 100μM Sal could downregulate the secretion of β-catenin in HFLS-RA induced by TNF-α.