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Interleukin-35 stimulates tumor necrosis factor-α activated osteoblasts differentiation through Wnt/β-catenin signaling pathway in rheumatoid arthritis.

Abstract：

:Interleukin (IL)-35 plays an important role in the pathogenesis of rheumatoid arthritis (RA), which is characterized by tumor necrosis factor (TNF)-α activated bone loss beginning early and persisting over time. The aim of this study was to explore the effects and signaling pathway of IL-35 on osteoblasts differentiation in MC3T3E1 cells and TNF-α activated MC3T3E1 cells. A microenvironment was established with low concentration and short-term treatment of TNF-α to mimic inflammatory activated osteoblasts of RA in vitro. The role of IL-35 on osteoblasts proliferation and apoptosis were assessed using cell counting kit (CCK)-8 assay and flow cytometry, respectively. Alkaline phosphatase (ALP) activity was measured by p-nitrophenyl phosphate assay. Extracellular matrix mineralization was measured by Alizarin red S staining. Osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) in response to IL-35 were investigated using real-time polymerase chain reaction and western blot analysis. Wnt/β-catenin signaling pathway in osteoblasts was investigated. In basal and TNF-α activated osteoblasts, IL-35 promoted proliferation and inhibited apoptosis. Basal and TNF-α activated ALP activity and mineralization in vitro was increased stimulated by IL-35. Furthermore, IL-35 increased the basal and TNF-α activated OPG expression and decreased basal and TNF-α activated RANKL expression. Blocking Wnt/β-catenin signaling pathway with Dickkopf (Dkk)-1 inhibited the osteogenic effects of IL-35. IL-35 stimulates basal and TNF-α activated osteoblasts differentiation through the Wnt/β-catenin signaling pathway, thus highlighting the IL-35 for pharmaceutical and medicinal applications for treating RA bone loss.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Li Y,Yuan L,Jiang S,Liu S,Xia L,Shen H,Lu J

doi

10.1016/j.intimp.2019.105810

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

105810

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(19)31119-1

journal_volume

pub_type

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Interleukin-35 stimulates tumor necrosis factor-α activated osteoblasts differentiation through Wnt/β-catenin signaling pathway in rheumatoid arthritis.