Izvorni znanstveni članak
https://doi.org/10.3325/cmj.2016.57.89
Interleukin 6/Wnt interactions in rheumatoid arthritis: interleukin 6 inhibits Wnt signaling in synovial fibroblasts and osteoblasts
Khrystyna Malysheva
; Department of Regulation of Cell Proliferation and Apoptosis Institute of Cell Biology of the National Academy of Sciences of Ukraine, Lviv, Ukraine
Karien de Rooij
; Leiden University Medical Center, Leiden, the Netherlands
Clemens W. G. M. Löwik
; Leiden University Medical Center, Leiden, the Netherlands
Dominique L. Baeten
; Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands
Stefan Rose-John
; Institute of Biochemistry, Christian-Albrechts-University, Kiel, Germany
Sažetak
Aim To evaluate the impact of previously unrecognized
negative interaction between the Wnt and interleukin (IL)
6 signaling pathways in skeletal tissues as a possible major
mechanism leading to age- and inflammation-related destruction
of bone and joints.
Methods Luciferase reporter assays were performed to
monitor Wnt pathway activation upon IL-6 and tumor necrosis
factor-α (TNFα) treatment. Functional contribution
of IL-6 and TNFα interaction to inhibition of bone formation
was evaluated in vitro using small hairpin RNAs (shRNA) in
mouse mesenchymal precursor cells (MPC) of C2C12 and
KS483 lines induced to differentiate into osteoblasts by
bone morphogenetic proteins (BMP).
Results IL-6 inhibited the activation of Wnt signaling in
primary human synoviocytes, and, together with TNFα
and Dickkopf-1, inhibited the activation of Wnt response.
ShRNA-mediated knockdown of IL-6 mRNA significantly increased
early BMP2/7-induced osteogenesis and rescued
it from the negative effect of TNFα in C2C12 cells, as well as
intensified bone matrix mineralization in KS483 cells.
Conclusion IL-6 is an important mediator in the inhibition
of osteoblast differentiation by TNFα, and knockdown of
IL-6 partially rescues osteogenesis from the negative control
of inflammation. The anti-osteoblastic effects of IL-6
are most likely mediated by its negative interaction with
Wnt signaling pathway
Ključne riječi
Hrčak ID:
169157
URI
Datum izdavanja:
15.4.2016.
Posjeta: 1.118 *