Affiliation:
1. Ganzhou Municipal Key Laboratory of Bone and Joint Research The Affiliated Ganzhou Hospital of Nanchang University Ganzhou 341000 China
2. Research Center of Translational Medicine Jinan Central Hospital Affiliated to Shandong First Medical University Jinan 250013 China
3. Department of Orthopedics Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310013 China
Abstract
AbstractThe pathophysiology of osteoarthritis (OA) is closely linked to autophagy abnormalities in articular chondrocytes, the sole mature cell type in healthy cartilage. Nevertheless, the precise molecular mechanism remains uncertain. Previous research has demonstrated that leptin activates mTORC1 , thereby inhibiting chondrocyte autophagy during the progression of OA. In this study, it is demonstrated that the presence of leptin induces a substantial increase in the expression of STAT3, leading to a notable decrease in REDD1 expression and subsequent phosphorylation of p70S6K, a recognized downstream effector of mTORC1. Conversely, inhibition of leptin yields contrasting effects. Additionally, the potential advantages of utilizing a sustained intra‐articular release of a leptin inhibitor (LI) via an injectable, thermosensitive poly(D,L‐lactide)‐poly(ethylene glycol)‐poly(D,L‐lactide) (PDLLA‐PEG‐PDLLA: PLEL) hydrogel delivery system for the purpose of investigating its impact on cartilage repair are explored. The study conducted on LI‐loaded PLEL (PLEL@LI) demonstrates remarkable efficacy in inhibiting OA and displays encouraging therapeutic advantages in the restoration of subchondral bone and cartilage. These findings establish a solid foundation for the advancement of a pioneering treatment approach utilizing PLEL@LI for OA.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Jiangxi Province
Science Fund for Distinguished Young Scholars of Jiangxi Province
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials