Histol Histopathol. 2021 Feb 15:18312. doi: 10.14670/HH-18-312. Online ahead of print.
ABSTRACT
OBJECTIVE: To investigate the expression of long-chain noncoding RNA GAS5 in osteoarthritis(OA) and the effect of silencing GAS5 on autophagy of osteoarthritis chondrocytes(OACs).
METHOD: OA rat models were constructed by cutting the anterior cruciate ligament, and the expressions of GAS5 in rat cartilage tissues at 4 weeks (early OA) and 12 weeks (late OA) after modeling were detected. The rat chondrocytes were isolated, cultured and transfected with si-GAS5 to silencing GAS5. Then, the changes of apoptosis and autophagy levels of OA chondrocytes were detected by transfection of GFP-LC3 and flow cytometry. Bioinformatic tools were used to analyze the miRNA binding to GAS5 and the downstream target genes, then luciferase reporter assay and GDC-0349 (inhibitor of mTOR) were used to verify their relationships.
RESULTS: The expressi on of GAS5 in cartilage tissue of OA rats was higher than control, which was higher in late OA than that in early OA. After silencing the GAS5, the autophagy ability of OACs was increased and the apoptosis rate was decreased. GAS5 was able to bind to miR-144 and regulate the expressin of mTOR. mTOR inhibitor GDC-0349 could reverse the inhibition of GAS5 on autophagy but could not reverse its effect on apoptosis.
CONCLUSION: GAS5 expresses highly in OA cartilage tissues and increases with the progression of OA. GAS5 inhibits autophagy and promotes the apoptosis of OACs, and the inhibition of autophagy may be related to its regulation of mTOR.
PMID:33586778 | DOI:10.14670/HH-18-312
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