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Biomaterials, Available online 10 June 2021, 120967 | https://doi.org/10.1016/j.biomaterials.2021.120967 Self-Assembled Hyaluronic Acid Nanoparticles for Osteoarthritis Treatment

Li-Jung Kang^a,b,c,1, Juhwan Yoon^d,1, Jun Gi Rho^d,e, Hwa Seung Han^f,g, Seulbi Lee^d, Young Soo Oh^h, Hwan Kimⁱ, Eunha Kim^d, Seok Jung Kim^j, Yong Taik Lim^c,f, Jae Hyung Park^f,k, Woo Keun Song^h, Siyoung Yang^a,b,c,*, Wook Kim^d,*

^aDepartment of Pharmacology, Ajou University School of Medicine, Suwon 16499, Republic of Korea
^bDegenerative InterDiseases Research Center, Ajou University School of Medicine, Suwon 16499, Republic of Korea
^cCIRNO, Sungkyunkwan University, Suwon, 16419, Republic of Korea
^dDepartment of Molecular Science & Technology, Ajou University, Suwon 16499, Republic of Korea
^ePharmaceutical Institute, FromBIO, Suwon 16681, Republic of Korea
^fSchool of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
^gNatural Product Informatics Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, Republic of Korea
^hCell Logistics Research Center, School of Life Science, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea
ⁱGIST Central Research Facilities, Bio Imaging Laboratory, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea
^jDepartment of Orthopaedic Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
^kBiomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea

¹These authors contributed equally to this work.

^*Corresponding author.

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 : hyaluronic acid, self-assembled nanoparticle, CD44, catabolic factor, osteoarthritis

논문정보

형식Research article
게재일2021년 06월 (BRIC 등록일 2021-06-16)
연구진국내 연구진
분야 의약학 > 분자세포의학

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