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Updated: Dec 3, 2025
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Precise targeting of miR-141/200c cluster in chondrocytes attenuates osteoarthritis development
Ming-Liang Ji1, Hua Jiang2, Fei Wu1
1The department of Orthopaedic Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
Objectives:
Despite preclinical studies involving miRNA therapeutics conducted in osteoarthritis (OA) over the years, none of these miRNAs have yet translated to clinical applications, owing largely to the lack of efficient intra-articular (IA) delivery systems. Here, we investigated therapeutic efficacy of the chondrocyte-specific aptamer-decorated PEGylated polyamidoamine nanoparticles (NPs)-based miRNAs delivery for OA.
Methods:
The role of miR-141/200c cluster during skeletal and OA development was examined by miR-141/200cflox/flox mice and Col2a1-CreERT2; miR-141/200cflox/flox mice. Histological analysis was performed in mouse joints and human cartilage specimens. Chondrocyte-specific aptamer-decorated NPs was designed, and its penetration, stability and safety were evaluated. OA progression was assessed by micro-CT analysis, X-ray and Osteoarthritis Research Society International scores after destabilising the medial meniscus surgery with miR-141/200c manipulation by NPs IA injection. Mass spectrometry analysis, molecular docking and molecular dynamics simulations were performed to investigate the interaction between aptamer and receptor.
Results:
Increased retention of NPs inside joint space is observed. The NPs are freely and deeply penetrant to mice and human cartilage, and unexpectedly persist in chondrocytes for at least 5 weeks. OA chondrocytes microenviroment improves endo/lysosomal escape of microRNAs (miRNAs). Therapeutically, IA injection of miR-141/200c inhibitors provides strong chondroprotection, whereas ectopic expression of miR-141/200c exacerbates OA. Mechanistically, miR-141/200c promotes OA by targeting SIRT1, which acetylates histone in the promoters of interleukin 6 (IL-6), thereby activating IL-6/STAT3 pathway.
Conclusions:
Our findings indicate that this nanocarrier can optimise the transport kinetics of miR-141/200c into chondrocytes, fostering miRNA-specific disease-modifying OA drugs development.
Insights
This study developed a novel nanoparticle delivery system for microRNAs (miRNAs) to treat osteoarthritis (OA). The system efficiently delivers miR-141/200c inhibitors, offering chondroprotection and advancing miRNA therapeutics for OA.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Osteoarthritis Research
Background:
- Current microRNA (miRNA) therapeutics for osteoarthritis (OA) face challenges due to inefficient intra-articular (IA) delivery systems.
- Preclinical studies have not yet translated to clinical applications, highlighting the need for improved delivery methods.
Purpose of the Study:
- To investigate the therapeutic efficacy of chondrocyte-specific aptamer-decorated PEGylated polyamidoamine nanoparticles (NPs) for miRNA delivery in OA.
- To develop an efficient IA delivery system for miRNA-based OA treatment.
Main Methods:
- Utilized miR-141/200cflox/flox mice and Col2a1-CreERT2; miR-141/200cflox/flox mice to examine miR-141/200c's role in OA.
- Designed and evaluated chondrocyte-specific aptamer-decorated NPs for penetration, stability, and safety.
- Assessed OA progression using micro-CT, X-ray, and OARSI scores after IA injection of NPs to manipulate miR-141/200c.
Main Results:
- NPs demonstrated increased retention in the joint space and deep penetration into mouse and human cartilage, persisting in chondrocytes for over 5 weeks.
- IA injection of miR-141/200c inhibitors showed significant chondroprotection, while its ectopic expression worsened OA.
- Mechanistically, miR-141/200c targets SIRT1, impacting the IL-6/STAT3 pathway in OA chondrocytes.
Conclusions:
- The developed nanocarrier effectively optimizes miR-141/200c transport into chondrocytes.
- This advancement fosters the development of miRNA-specific, disease-modifying OA drugs.
