[논문/Biomaterials] Self-assembled hyaluronic acid nanoparticles for osteoarthritis treatment

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    2021-10-20 14:51
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KIURI 강이중 참여연구원 논문

 

Biomaterials. 2021 Aug;275:120967. doi: 10.1016/j.biomaterials.2021.120967. Epub 2021 Jun 10.

 

Self-assembled hyaluronic acid nanoparticles for osteoarthritis treatment.

 

Although osteoarthritis (OA) is the most prevalent degenerative joint disease, there is no effective disease-modifying therapy. We report an empty self-assembled hyaluronic acid nanoparticle (HA-NP) as a potential therapeutic agent for OA treatment. In mouse primary articular chondrocytes, HA-NPs blocked the receptor-mediated cellular uptake of free low-molecular-weight HA, and the cellular uptake of HA-NPs increased by ectopic expression of CD44, using an adenoviral delivery system (Ad-Cd44). HA-NP showed in vitro resistance to digestion with hyaluronidase and in vivo long-term retention ability in knee joint, compared with free high-molecular-weight (HMW) HA. CD44 expression increased in the damaged articular cartilage of patients and mice with OA. Ad-Cd44 infection and IL-1β treatment induced in vitro phenotypes of OA by enhancing catabolic gene expression in primary articular chondrocytes, and these effects were attenuated by HA-NP, but not HMW HA. Both Cd44 deficiency and intra-articular injection of HA-NP protected joint cartilage against OA development in the OA mouse model. NF-κB was found to mediate CD44-induced catabolic factor expression and HA-NP inhibited CD44-induced NF-κB activation in chondrocytes. Our results identify an empty HA-NP as a potential therapeutic agent targeting CD44 for OA treatment, and the CD44-NF-κB-catabolic gene axis as an underlying mechanism of destructive cartilage disorders.

 

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