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Journal of Molecular Medicine

, Volume 96, Issue 6, pp 495–511 | Cite as

CUL4B promotes the pathology of adjuvant-induced arthritis in rats through the canonical Wnt signaling

  • Chenggui Miao
  • Jun Chang
  • Guoxue Zhang
  • Hao Yu
  • Lili Zhou
  • Guoliang Zhou
  • Chuanlei Zhao
Original Article
  • 139 Downloads

Abstract

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.

Key messages

  • 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 Rheumatoid arthritis Adjuvant-induced arthritis Canonical Wnt signaling miR-101-3p 

Abbreviations

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

MTT

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide

DMSO

dimethyl sulfoxide

FBS

fetal bovine serum

WDR5

WD repeat containing protein5

PrxIII

peroxiredoxin III

SDF-1

stromal cell derived factor 1

Notes

Compliance with ethical standards

Conflict of interest statement

The authors declare no competing interests.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Chenggui Miao
    • 1
  • Jun Chang
    • 2
  • Guoxue Zhang
    • 3
  • Hao Yu
    • 1
  • Lili Zhou
    • 1
  • Guoliang Zhou
    • 1
  • Chuanlei Zhao
    • 1
  1. 1.Department of Pharmacy, School of Life and Health ScienceAnhui Science and Technology UniversityFengyangChina
  2. 2.Department of Orthopaedics, 4th Affiliated HospitalAnhui Medical UniversityHefeiChina
  3. 3.State Key Laboratory of Tea Biology and Resource Utilization, College of Tea and Food Science and TechnologyAnhui Agricultural UniversityHefeiChina

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