Expression of Long-Chain Noncoding RNA GAS5 in Osteoarthritis And Its Effect on Apoptosis And Autophagy of Osteoarthritis Chondrocytes

Abstract

Objective: To investigate the expression of long chain non-coding RNA GAS5 in osteoarthritis(OA) and the effect on autophagy and apoptosis of chondrocytes. Method: OA rat model was constructed and the expressions of GAS5 in articular cartilage tissues at 4 weeks(early OA) and 12 weeks(late OA) after modeling were detected. The chondrocytes of OA rat were isolated, cultured and transfected with si-GAS5 to silence the GAS5. Then the change of apoptosis and autophagy levels of OA chondrocytes were detected. The microRNA binding to GAS5 and the competitive target gene were analyzed and verified. Results: The expression of GAS5 in cartilage tissue of OA rats was higher than that of control, which was higher in late OA than that in early OA. After silencing the GAS5, the autophagy ability of OA chondrocytes was increased and the apoptosis rate was decreased. GAS5 could bind with miR-144 competitively and regulate mTOR positively. The mTOR inhibitor GDC-0349 could reverse the inhibition of GAS5 on cell autophagy but could not reverse the promotion on apoptosis. Conclusion: GAS5 expression was high and increased with the progression of OA. GAS5 could inhibit the autophagy and promote the apoptosis of OA chondrocytes, and the effect on autophagy may be related to the regulation on mTOR.

Identification of inflammation related miRNA, lncRNA and mRNA in synovial tissue of knee osteoarthritis patients

“…Studies have shown that lncRNA GAS5 is highly expressed in OA cartilage and increases with the progress of OA. GAS5 inhibits autophagy and promotes apoptosis of chondrocytes, which may be related to miR-34a / Bcl-2 axis or mTOR [35,36]. Similarly, LINC02288 expression was signi cantly up-regulated in OA rat model.…”

Long non-coding RNA HOTAIRincreased mechanical stimulation-induced apoptosis by regulating microRNA-221/BBC3 axis in C28/I2 cells

“…LncRNA GAS5 expression is up regulated in OA cartilage tissues. Silence of GAS5 increases the autophagy ability and decreases the apoptosis rate by sponging miR-144 [ 25 ]. In addition, the increased expression of lncRNA PVT1 in diabetic OA cartilage is also associated with Mankin score and reduced expression of type II collagen by negatively interacting with miR-146a, increasing the productions of inflammatory cytokines, and activating TGFβ/SMAD4 signaling pathway [ 26 ].…”

Xanthohumol Inhibited Mechanical Stimulation-Induced Articular ECM Degradation by Mediating lncRNA GAS5/miR-27a Axis

“…LncRNA GAS5 expression is up regulated in OA cartilage tissues. Silence of GAS5 increases the autophagy ability and decreases the apoptosis rate by sponging miR-144 ( Ji et al, 2021 ). Similarly, our study also demonstrated that GAS5 expression was significantly increased by mechanical stimulation in vivo and in vitro .…”