An Injectable Sustained Release Hydrogel of Hyaluronic Acid Loaded with β‐Ecdysterone Ameliorates Cartilage Damage in Osteoarthritis via Activating Autophagy

Abstract This study uses the knee Osteoarthritis (OA) rat (constructed by the anterior cruciate ligament transection) and the inflammatory chondrocyte (constructed by 20 ng mL −1 tumor necrosis factor‐α (TNF‐α)) to study the improvement effect of injectable β‐ecdysterone (β‐Ec) hydrogel consisting of poly (D, L‐lactic‐co‐glycolic acid)‐hyaluronate (HA‐β‐Ec‐Gel) on cartilage damage. The results show that the HA‐β‐Ec‐Gel improves the three‐dimensional of bone structure. The HA‐β‐Ec‐Gel treatment improves cartilage tissue injury of OA rats. It advances the levels of autophagic factor Beclin1 (Beclin1) and microtubule–associated protein 1 light chain 3 (LC3) in cartilage tissue. The lysyl oxidase like 3 (LOXL3), ras homologue enriched (Rheb), phosphorylated (p)‐V–akt murine thymoma viral oncogene homolog (AKT)/AKT, and p‐mechanistic target of rapamycin (mTOR)/mTOR signal expression are inhibited by HA‐β‐Ec‐Gel intervention. In inflammatory chondrocytes, β‐Ec improves the cell viability, autophagosome numbers, and Beclin1 and LC3 II/I levels, also inhibits apoptotic rate, LOXL3 and Rheb expression levels, and the AKT/mTOR pathway. The 3‐methyladenine addition reverses these effects of β‐Ec. The Rheb or LOXL3 knockdown chondrocytes aren't sensitive to TNF–α‐induced damage. Their autophagy level is high. This study reveals the improvement effects of injectable HA‐β‐Ec‐Gel on OA, which provides a scientific basis and new direction for the development of OA treatment strategies.