LncRNA ZFAS1 protects chondrocytes from IL-1β-induced apoptosis and extracellular matrix degradation via regulating miR-7-5p/FLRT2 axis.
Chondrocytes
FLRT2
Osteoarthritis
ZFAS1
miR-7-5p
Journal
Journal of orthopaedic surgery and research
ISSN: 1749-799X
Titre abrégé: J Orthop Surg Res
Pays: England
ID NLM: 101265112
Informations de publication
Date de publication:
25 Apr 2023
25 Apr 2023
Historique:
received:
25
11
2022
accepted:
14
04
2023
medline:
27
4
2023
pubmed:
26
4
2023
entrez:
25
4
2023
Statut:
epublish
Résumé
Increasing evidence suggested that long non-coding RNAs (lncRNAs) played vital roles in osteoarthritis (OA) progression. In this study, we aimed to reveal the protective roles of lncRNA ZFAS1 in osteoarthritis (OA) and further investigated its underlying mechanism. The chondrocytes were stimulated by IL-1β to establish an in vitro OA model. Then, the expression of ZFAS1, miR-7-5p, and FLRT2 in chondrocytes was determined by qRT-PCR. Gain- and loss-of-function assays of ZFAS1, miR-7-5p and FLRT2 were conducted. CCK-8 assay and flow cytometry analysis were performed to detect cell viability and apoptosis rate. The expression levels of cartilage-related proteins, including MMP13, ADAMTS5, Collagen II, and Aggrecan, were measured by western blot analysis. The interaction between ZFAS1 and miR-7-5p, as well as miR-7-5p and FLRT2, was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. The expression of ZFAS1 and FLRT2 was down-regulated, while the expression of miR-7-5p was up-regulated in chondrocytes exposed to IL-1β. ZFAS1 overexpression promoted cell viability and suppressed apoptosis in IL-1β-treated chondrocytes. Besides, ZFAS1 overexpression suppressed the expression of MMP13 and ADAMTS5, but promoted the expression of Collagen II and Aggrecan to suppress ECM degradation. The mechanistic study showed that ZFAS1 sponged miR-7-5p to regulate FLRT2 expression. Furthermore, the overexpression of miR-7-5p could neutralize the effect of ZFAS1 in IL-1β-treated chondrocytes, and suppression of FLRT2 counteracted the miR-7-5p down-regulation role in IL-1β-treated chondrocytes. ZFAS1 could promote cell viability of IL-1β-treated chondrocytes via regulating miR-7-5p/FLRT2 axis. Trial registration Not applicable.
Sections du résumé
BACKGROUND
BACKGROUND
Increasing evidence suggested that long non-coding RNAs (lncRNAs) played vital roles in osteoarthritis (OA) progression. In this study, we aimed to reveal the protective roles of lncRNA ZFAS1 in osteoarthritis (OA) and further investigated its underlying mechanism.
METHODS
METHODS
The chondrocytes were stimulated by IL-1β to establish an in vitro OA model. Then, the expression of ZFAS1, miR-7-5p, and FLRT2 in chondrocytes was determined by qRT-PCR. Gain- and loss-of-function assays of ZFAS1, miR-7-5p and FLRT2 were conducted. CCK-8 assay and flow cytometry analysis were performed to detect cell viability and apoptosis rate. The expression levels of cartilage-related proteins, including MMP13, ADAMTS5, Collagen II, and Aggrecan, were measured by western blot analysis. The interaction between ZFAS1 and miR-7-5p, as well as miR-7-5p and FLRT2, was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay.
RESULTS
RESULTS
The expression of ZFAS1 and FLRT2 was down-regulated, while the expression of miR-7-5p was up-regulated in chondrocytes exposed to IL-1β. ZFAS1 overexpression promoted cell viability and suppressed apoptosis in IL-1β-treated chondrocytes. Besides, ZFAS1 overexpression suppressed the expression of MMP13 and ADAMTS5, but promoted the expression of Collagen II and Aggrecan to suppress ECM degradation. The mechanistic study showed that ZFAS1 sponged miR-7-5p to regulate FLRT2 expression. Furthermore, the overexpression of miR-7-5p could neutralize the effect of ZFAS1 in IL-1β-treated chondrocytes, and suppression of FLRT2 counteracted the miR-7-5p down-regulation role in IL-1β-treated chondrocytes.
CONCLUSIONS
CONCLUSIONS
ZFAS1 could promote cell viability of IL-1β-treated chondrocytes via regulating miR-7-5p/FLRT2 axis. Trial registration Not applicable.
Identifiants
pubmed: 37098630
doi: 10.1186/s13018-023-03802-9
pii: 10.1186/s13018-023-03802-9
pmc: PMC10131303
doi:
Substances chimiques
RNA, Long Noncoding
0
Matrix Metalloproteinase 13
EC 3.4.24.-
Aggrecans
0
MicroRNAs
0
Interleukin-1beta
0
MIRN7 microRNA, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
320Informations de copyright
© 2023. The Author(s).
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