2. Academic Validation
  3. Self-assembled hyaluronic acid nanoparticles for osteoarthritis treatment

Self-assembled hyaluronic acid nanoparticles for osteoarthritis treatment

  • Biomaterials. 2021 Aug:275:120967. doi: 10.1016/j.biomaterials.2021.120967.
Li-Jung Kang 1,  Juhwan Yoon 2,  Jun Gi Rho 3,  Hwa Seung Han 4,  Seulbi Lee 2,  Young Soo Oh 5,  Hwan Kim 6,  Eunha Kim 2,  Seok Jung Kim 7,  Yong Taik Lim 8,  Jae Hyung Park 9,  Woo Keun Song 5,  Siyoung Yang 10,  Wook Kim 11
Affiliations

Affiliations

  • 1 Department of Pharmacology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea; Degenerative InterDiseases Research Center, Ajou University School of Medicine, Suwon, 16499, Republic of Korea; CIRNO, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
  • 2 Department of Molecular Science & Technology, Ajou University, Suwon, 16499, Republic of Korea.
  • 3 Department of Molecular Science & Technology, Ajou University, Suwon, 16499, Republic of Korea; Pharmaceutical Institute, FromBIO, Suwon, 16681, Republic of Korea.
  • 4 School of Chemical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea; Natural Product Informatics Research Center, Korea Institute of Science and Technology (KIST), Gangneung, 25451, Republic of Korea.
  • 5 Cell Logistics Research Center, School of Life Science, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.
  • 6 GIST Central Research Facilities, Bio Imaging Laboratory, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.
  • 7 Department of Orthopaedic Surgery, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.
  • 8 CIRNO, Sungkyunkwan University, Suwon, 16419, Republic of Korea; School of Chemical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
  • 9 School of Chemical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea; Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon, 16419, Republic of Korea.
  • 10 Department of Pharmacology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea; Degenerative InterDiseases Research Center, Ajou University School of Medicine, Suwon, 16499, Republic of Korea; CIRNO, Sungkyunkwan University, Suwon, 16419, Republic of Korea. Electronic address: [email protected].
  • 11 Department of Molecular Science & Technology, Ajou University, Suwon, 16499, Republic of Korea. Electronic address: [email protected].
PMID: 34153786 DOI: 10.1016/j.biomaterials.2021.120967
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.

Keywords

CD44; Catabolic factor; Hyaluronic acid; Osteoarthritis; Self-assembled nanoparticle.

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