CUL4B promotes the pathology of adjuvant-induced arthritis in rats
through the canonical Wnt signaling
Received: 5 August 2017 /Revised: 7 February 2018 /Accepted: 22 March 2018 /Published online: 6 April 2018
Springer-Verlag GmbH Germany, part of Springer Nature 2018
This work aims to discuss the possibility that disordered CUL4B was involved in the pathogenesis of adjuvant-induced arthritis
(AIA) in rats. Synovium and FLS from AIA rats both showed increased CUL4B and β-catenin, and up-regulated CUL4B
enhanced the canonical Wnt signaling by targeting the GSK3β. Increased CUL4B promoted the FLS abnormal proliferation,
activated the secretion of IL-1β and IL-8, and promoted the production of AIA pathology gene MMP3 and fibronectin.
Furthermore, miR-101-3p was significantly down-regulated in AIA rats compared with controls, and transfection of AIA FLS
with miR-101-3p mimics significantly down-regulated the CUL4B expression, whereas transfection with miR-101-3p inhibitors
resulted in an opposite observation. The dual-luciferase reporter assay confirmed that the CUL4B was a direct target of miR-101-
3p, and further analysis suggested that lowly expressed miR-101-3p contributed to disordered CUL4B activating the canonical
Wnt signaling pathway and further promoting the development of AIA rats. Thus clarification of the CUL4B roles in the
pathogenesis of AIA rats and corresponding mechanisms will contribute to the disease diagnosis and treatment for rheumatoid
arthritis (RA) patients.
& CUL4B expression is up-regulated in synovium and FLS from AIA rats.
& Increased CUL4B promotes the canonical Wnt signaling.
& Increased CUL4B promotes the pathogenesis of AIA rats.
& Decreased miR-101-3p contributes to disordered CUL4B.
Keywords Cullin 4B
Canonical Wnt signaling
RA rheumatoid arthritis
CUL4B Cullin 4B
AIA adjuvant-induced arthritis
RING really interesting new gene
CRLs Cullin-RING ubiquitin ligase
PRC2 polycomb repressive complex 2
DMSO dimethyl sulfoxide
FBS fetal bovine serum
WDR5 WD repeat containing protein5
PrxIII peroxiredoxin III
SDF-1 stromal cell derived factor 1
Cullin-really interesting new gene (RING) ubiquitin ligase
(CRLs) is the largest E3 ubiquitin ligase family in eukaryotes,
which is associated with cell cycle, signal transduction, DNA
damage response, gene expression, chromatin remodeling,
* Chenggui Miao
Department of Pharmacy, School of Life and Health Science, Anhui
Science and Technology University, Donghua Road,
Fengyang 233100, Anhui Province, China
Department of Orthopaedics, 4th Affiliated Hospital, Anhui Medical
University, Hefei 230032, China
State Key Laboratory of Tea Biology and Resource Utilization,
College of Tea and Food Science and Technology, Anhui
Agricultural University, Hefei 230036, China
Journal of Molecular Medicine (2018) 96:495–511