Open Access
ARTICLE
Bioinformatic analysis of lncRNA-associated competing endogenous RNA regulatory networks in synovial tissue of temporomandibular joint osteoarthritis
CHUYAO WANG1,2,#, CHUAN LU2,#, LUXIANG ZOU2,*, DONGMEI HE2,*
1 School of Stomatology, Qingdao University, Qingdao, 266000, China
2 Department of Oral Surgery, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai
Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai, 200011, China
* Corresponding Author: Dongmei He,
# Co-first authors
(This article belongs to this Special Issue: Bioinformatics Study of Diseases)
BIOCELL 2023, 47(6), 1293-1306. https://doi.org/10.32604/biocell.2023.028199
Received 04 December 2022; Accepted 15 February 2023; Issue published 19 May 2023
Abstract
Background: Temporomandibular joint osteoarthritis (TMJOA) is an end-stage disease that seriously affects
the patients’ quality of life. Molecular insights in advancing our understanding of TMJOA are the need of the hour.
Methods: We performed RNA high-throughput sequencing and bioinformatics analysis of differentially expressed
(DE) long non-coding RNA (lncRNAs), microRNAs (miRNAs), and messenger RNA (mRNAs) in human synovial
TMJOA tissues. Firstly, synovium samples of TMJOA patients and non-TMJOA controls were collected for highthroughput sequencing of lncRNAs, miRNAs, and mRNAs. We then performed biological function analysis of the top
100 mRNAs with more than 2-fold differential expression, and their upstream regulated miRNAs and lncRNAs were
predicted separately. Intersections between predicted miRNAs/lncRNAs and differentially expressed miRNAs/
lncRNAs were determined, respectively. Regulatory networks among the selected lncRNAs, miRNAs, and mRNAs
were constructed. Finally, Western Blotting and reverse transcription-quantitative polymerase chain reaction (RTqPCR) were used to explore the function of selected lncRNA and mRNAs.
Results: Our analysis showed that the only
upregulated lncRNAxist, was involved in intracellular protein degradation, cartilage matrix degradation, and osteoclast
differentiation through four regulatory axes:
miR-1271-5p/ctsb,
miR-365a-3p/mmp3,
miR-199a-3p/fos, and
miR-27b-3p/
miR-1271-5p/grb2. RT-qPCR results showed that
xist expression increased in both TMJOA synovial tissue and
inflammatory-stimulated synovial cells. Inhibition of
xist could promote the proliferation of synovial cells upon
inflammatory stimulation, and
xist could positively regulate the expression of GRB2. Targeting GRB2 could inhibit
the expression of matrix degrading enzymes in synovial cells, thereby attenuating the inflammatory environment.
Conclusion: Given the current lack of reports of lncRNA regulation in TMJOA synovitis, our results revealed that
xist was significantly differentially expressed in human synovial TMJOA and could regulate the expression of GRB2,
which may play a role in the progression of TMJOA.
Keywords
Cite This Article
WANG, C., LU, C., ZOU, L., HE, D. (2023). Bioinformatic analysis of lncRNA-associated competing endogenous RNA regulatory networks in synovial tissue of temporomandibular joint osteoarthritis.
BIOCELL, 47(6), 1293–1306. https://doi.org/10.32604/biocell.2023.028199