Full Papers
Histone deacetylase 1 is increased in rheumatoid arthritis synovium and promotes synovial cell hyperplasia and synovial inflammation in the collagen-induced arthritis mouse model via the microRNA-124-dependent MARCKS-JAK/STAT axis
Q. Meng1, B. Pan2, P. Sheng3
- Department of Joint Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangdong, China.
- Department of Joint Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangdong, China.
- Department of Joint Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangdong, China. shengpy@mail.sysu.edu.cn
CER13476
2021 Vol.39, N°5
PI 0970, PF 0981
Full Papers
PMID: 33337986 [PubMed]
Received: 21/04/2020
Accepted : 31/08/2020
In Press: 04/12/2020
Published: 31/08/2021
Abstract
OBJECTIVES:
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease featured by synovial joint inflammation. Increasing evidence has highlighted microRNAs (miRNAs) and histone deacetylase 1 (HDAC1) as active participants in RA progression. Hence, the present study aims to explore the functions of HDAC1 and miR-124 on synovial cell hyperplasia and synovial inflammation in RA.
METHODS:
The expression of HDAC1, miR-124 and MARCKS was determined in the synovial tissues collected from 25 RA patients by RT-qPCR and Western blot analysis. Next, a mouse model with collagen-induced arthritis (CIA) was established, from which fibroblast-like synovial cells (FLSs) were isolated. Then the effect of HDAC1, miR-124 and MARCKS on synovial cell hyperplasia and synovial inflammation in CIA mice was evaluated by HE staining, ELISA, and EdU assays. Afterwards, the interaction among HDAC1, miR-124, MARCKS and the JAK/STAT signalling pathway was assessed by ChIP and dual luciferase reporter assay. Finally, the effect of HDAC1 on RA was further verified by establishing a CIA mouse model.
RESULTS:
HDAC1 was highly expressed and miR-124 and MARCKS were poorly expressed in synovial tissues of CIA. Silencing HDAC1 inhibited synovial cell hyperplasia and synovial inflammation by elevating MARCKS and miR-124 both in vitro and in vivo. Deficiency of HDAC1 promoted H3 and H4 acetylation of miR-124 and MARCKS promoter region. miR-124 alleviated synovial cell hyperplasia and synovial inflammation by repressing the JAK/STAT signalling pathway in CIA.
CONCLUSIONS:
To sum up, silencing HDAC1 mitigates synovial cell hyperplasia and synovial inflammation in mice with CIA by elevating miR-124 and MARCKS expression, thus highlighting a promising competitive new target for RA treatment.
