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Self-assembled hyaluronic acid nanoparticles for osteoarthritis treatment

Authors :
Woo Keun Song
Siyoung Yang
Hwan Kim
Eunha Kim
Young Soo Oh
Jun Gi Rho
Juhwan Yoon
Wook Kim
Yong Taik Lim
Jae Hyung Park
Seulbi Lee
Seok Jung Kim
Li-Jung Kang
Hwa Seung Han
Source :
Biomaterials. 275:120967
Publication Year :
2021
Publisher :
Elsevier BV, 2021.

Abstract

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.

Details

ISSN :
01429612
Volume :
275
Database :
OpenAIRE
Journal :
Biomaterials
Accession number :
edsair.doi.dedup.....6212a1c0886256a169ffe29c8baa2971
Full Text :
https://doi.org/10.1016/j.biomaterials.2021.120967