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Open AccessArticle

Induction of WNT16 via Peptide-mRNA Nanoparticle-Based Delivery Maintains Cartilage Homeostasis

1
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
2
John Cochran Veterans Affairs Medical Center, St. Louis, MO 63106, USA
3
Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
4
Department of Cardiovascular Sciences, University of South Florida, Tampa, FL 33620, USA
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2020, 12(1), 73; https://doi.org/10.3390/pharmaceutics12010073
Received: 21 November 2019 / Revised: 27 December 2019 / Accepted: 13 January 2020 / Published: 17 January 2020
(This article belongs to the Special Issue Nanotechnology-Based Approaches for Chronic Diseases)
Osteoarthritis (OA) is a progressive joint disease that causes significant disability and pain and for which there are limited treatment options. We posit that delivery of anabolic factors that protect and maintain cartilage homeostasis will halt or retard OA progression. We employ a peptide-based nanoplatform to deliver Wingless and the name Int-1 (WNT) 16 messenger RNA (mRNA) to human cartilage explants. The peptide forms a self-assembled nanocomplex of approximately 65 nm in size when incubated with WNT16 mRNA. The complex is further stabilized with hyaluronic acid (HA) for enhanced cellular uptake. Delivery of peptide-WNT16 mRNA nanocomplex to human cartilage explants antagonizes canonical β-catenin/WNT3a signaling, leading to increased lubricin production and decreased chondrocyte apoptosis. This is a proof-of-concept study showing that mRNA can be efficiently delivered to articular cartilage, an avascular tissue that is poorly accessible even when drugs are intra-articularly (IA) administered. The ability to accommodate a wide range of oligonucleotides suggests that this platform may find use in a broad range of clinical applications. View Full-Text
Keywords: nanoparticle; mRNA delivery; osteoarthritis nanoparticle; mRNA delivery; osteoarthritis
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MDPI and ACS Style

Yan, H.; Hu, Y.; Akk, A.; Rai, M.F.; Pan, H.; Wickline, S.A.; Pham, C.T. Induction of WNT16 via Peptide-mRNA Nanoparticle-Based Delivery Maintains Cartilage Homeostasis. Pharmaceutics 2020, 12, 73.

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