Cartilage targeting hydrogel nanoplatform degrades BRD4 to alleviate osteoarthritis via 1 Nav1.7 axis
Published in Bioengineering & Biotechnology, Materials, and Biomedical Research
It is confirmed that BRD4/Nav1.7 axis drives inflammatory and metabolic dysfunction in OA. BRD4 as a key regulator that enhances Nav1.7 transcription, promoting mitochondrial impairment and catabolic activation in chondrocytes. Develop a biomimetic hydrogel system incorporating chondrocyte membrane-coated nanoparticles for cartilage-specific delivery of a BRD4 proteolysis-targeting chimera (PROTAC).
This nanoplatform enables efficient intra-articular delivery, immune evasion and targeted retention in cartilage.
Treatment suppresses inflammatory responses, restores mitochondrial function and reduces cartilage degeneration and pain behaviors in two mouse models of OA.
These findings establish targeted BRD4 degradation as a disease-modifying strategy and provide a precision nanotherapeutic platform for OA.
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Developed cartilage-targeting hydrogel delivering BRD4-degrading PROTACs
can treat arthritis very effective, own clinical translation prospects.