Paper Information

Journal:   IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES   MAY 2018 , Volume 21 , Number 5; Page(s) 529 To 535.
 
Paper: 

DOWN-REGULATION OF MICRORNA-23B AGGRAVATES LPS-INDUCED INFLAMMATORY INJURY IN CHONDROGENIC ATDC5 CELLS BY TARGETING PDCD4

 
 
Author(s):  YANG ZHONGMENG*, TANG YUXING, ZHAO QING, LU HUADING, XU GUOYONG
 
* DEPARTMENT OF ORTHOPEDICS, THE FIFTH AFFILIATED HOSPITAL OF SUN YAT-SEN UNIVERSITY, ZHUHAI, GUANGDONG 519000, CHINA
 
Abstract: 

Objective (s): Osteoarthritis (OA), characterized by degradation of articular cartilage, is a leading cause of disability. As the only cell type present in cartilage, chondrocytes play curial roles in the progression of OA. In our study, we aimed to explore the roles of miR-23b in the lipopolysaccharide (LPS) -induced inflammatory injury.
Materials and Methods: LPS-induced cell injury of ATDC5 cells was evaluated by the loss of cell viability, enhancement of cell apoptosis, alteration of apoptosis-associated proteins, and release of inflammatory cytokines. Then, miR-23b level after LPS treatment was assessed by qRT-PCR. Next, the effects of aberrantly expressed miR-23b on the LPS-induced inflammatory injury were explored. The possible target genes of miR-23b were virtually screened by informatics and verified by luciferase assay. Subsequently, whether miR- 23b functioned through regulating the target gene was validated. The involved signaling pathways were investigated finally.
Results: Cell viability was decreased but cell apoptosis, as well as release of inflammatory cytokines, was enhanced by LPS treatment. MiR-23b was down-regulated by LPS and its overexpression alleviated LPS-induced inflammatory injury. PDCD4, negatively regulated by miR-23b expression, was verified as a target gene of miR-23b. Following experiments showed miR-23b alleviated LPS-induced cell injury through down-regulating PDCD4 expression. Phosphorylated levels of key kinases in the NF-kB pathway, as well as expressions of key kinases in the Notch pathways, were increased by PDCD4 overexpression.
Conclusion: MiR-23b was down-regulated after LPS treatment, and its overexpression ameliorated LPS-induced inflammatory injury in ATDC5 cells by targeting PDCD4, which could activate the NF-kB/ Notch pathways.

 
Keyword(s): INFLAMMATORY INJURY, MICRORNA-23B, NF-κB/NOTCH, OSTEOARTHRITIS, PDCD4
 
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