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Self-assembled hyaluronic acid nanoparticles for osteoarthritis treatment
- 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.
- Subjects :
- Cartilage, Articular
Cartilage disorder
Biophysics
Bioengineering
02 engineering and technology
Osteoarthritis
Pharmacology
Biomaterials
Mice
03 medical and health sciences
chemistry.chemical_compound
Chondrocytes
In vivo
Hyaluronidase
Gene expression
Hyaluronic acid
medicine
Animals
Humans
Hyaluronic Acid
030304 developmental biology
0303 health sciences
biology
Chemistry
CD44
021001 nanoscience & nanotechnology
medicine.disease
Mechanics of Materials
Ceramics and Composites
biology.protein
Nanoparticles
Ectopic expression
0210 nano-technology
medicine.drug
Subjects
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