Delivery of Chondrocyte-Targeting sh-TTTY15 (Testis-Specific Transcript, Y-Linked 15) Nanoparticles Against LncRNA TTTY15 Improves Osteoarthritis by Regulating Autophagy and Oxidative Stress

Abstract

Objective: To explore the potential role of hyaluronic acid-modified peptide-lncRNA TTTY15 nanoparticles in joint injury of chondrocytes in OA rats. Methods: Cell proliferation, apoptosis and oxidative stress were tested by CCK8, flow cytometry and biochemical analysis. Histopathology and LC3 expression were analyzed by HE, TUNEL and IF. The expression levels of TTTY15, LC3, p62, c-caspase3, Col2A1, ACAN, ADAMTS-5 and MMP13 were tested by RT–qPCR, western blotting and IHC. Autophagosomes were observed by TEM. Results: Bioinformatics and RT–PCR analyses showed that TTTY15 was highly expressed in OA- and TBHP-stimulated chondrocytes. Ov-TTTY15 aggravated TBHP-induced activity decreases, apoptosis, oxidative stress, ECM degradation and autophagic flux reduction in chondrocytes. HA-coated-p5RHH-sh-TTTY15 nanoparticle intervention enhanced the stability and prolonged TTTY15 silencing in chondrocytes. HA-coated-p5RHH-sh-TTTY15 nanoparticles inhibited TBHP-induced C-28/I2 cell damage and activated autophagy, and the inhibitory effect was greater than that of sh-TTTY15. Conclusion: HA-coated-p5RHH-sh-TTTY15 nanoparticles enhanced the stable silencing of TTTY15 in chondrocytes; promoted cell proliferation; inhibited apoptosis, oxidative stress and ECM degradation; and activated autophagy to improve joint injury in OA rats.