Next Article in Journal
Phonon Bridge Effect in Superlattices of Thermoelectric TiNiSn/HfNiSn With Controlled Interface Intermixing
Next Article in Special Issue
Nanomedicine and Onco-Immunotherapy: From the Bench to Bedside to Biomarkers
Previous Article in Journal
Exploration of the Interaction Strength at the Interface of Anionic Chalcogen Anchors and Gold (111)-Based Nanomaterials
Previous Article in Special Issue
In-Situ Biofabrication of Silver Nanoparticles in Ceiba pentandra Natural Fiber Using Entada spiralis Extract with Their Antibacterial and Catalytic Dye Reduction Properties
Article

Therapeutic Delivery of rAAV sox9 via Polymeric Micelles Counteracts the Effects of Osteoarthritis-Associated Inflammatory Cytokines in Human Articular Chondrocytes

1
Center of Experimental Orthopaedics, Saarland University Medical Center, D-66421 Homburg, Germany
2
Cell Therapy and Regenerative Medicine Unit, Centro de Investigacións Científicas Avanzadas (CICA), Universidade da Coruña, ES-15071 A Coruña, Spain
*
Author to whom correspondence should be addressed.
Nanomaterials 2020, 10(6), 1238; https://doi.org/10.3390/nano10061238
Received: 1 June 2020 / Revised: 22 June 2020 / Accepted: 22 June 2020 / Published: 25 June 2020
(This article belongs to the Special Issue Advances in Nanomaterials in Biomedicine)
Osteoarthritis (OA) is a prevalent joint disease linked to the irreversible degradation of key extracellular cartilage matrix (ECM) components (proteoglycans, type-II collagen) by proteolytic enzymes due to an impaired tissue homeostasis, with the critical involvement of OA-associated pro-inflammatory cytokines (interleukin 1 beta, i.e., IL-1β, and tumor necrosis factor alpha, i.e., TNF-α). Gene therapy provides effective means to re-establish such degraded ECM compounds by rejuvenating the altered OA phenotype of the articular chondrocytes, the unique cell population ubiquitous in the articular cartilage. In particular, overexpression of the highly specialized SOX9 transcription factor via recombinant adeno-associated viral (rAAV) vectors has been reported for its ability to readjust the metabolic balance in OA, in particular via controlled rAAV delivery using polymeric micelles as carriers to prevent a possible vector neutralization by antibodies present in the joints of patients. As little is known on the challenging effects of such naturally occurring OA-associated pro-inflammatory cytokines on such rAAV/polymeric gene transfer, we explored the capacity of polyethylene oxide (PEO) and polypropylene oxide (PPO)-based polymeric micelles to deliver a candidate rAAV-FLAG-hsox9 construct in human OA chondrocytes in the presence of IL-1β and TNF-α. We report that effective, micelle-guided rAAV sox9 overexpression enhanced the deposition of ECM components and the levels of cell survival, while advantageously reversing the deleterious effects afforded by the OA cytokines on these processes. These findings highlight the potentiality of polymeric micelles as effective rAAV controlled delivery systems to counterbalance the specific contribution of major OA-associated inflammatory cytokines, supporting the concept of using such systems for the treatment for chronic inflammatory diseases like OA. View Full-Text
Keywords: osteoarthritis; human articular cartilage; rAAV vectors; SOX9; polymeric micelles; pro-inflammatory cytokines; IL-1β; TNF-α osteoarthritis; human articular cartilage; rAAV vectors; SOX9; polymeric micelles; pro-inflammatory cytokines; IL-1β; TNF-α
Show Figures

Graphical abstract

MDPI and ACS Style

Urich, J.; Cucchiarini, M.; Rey-Rico, A. Therapeutic Delivery of rAAV sox9 via Polymeric Micelles Counteracts the Effects of Osteoarthritis-Associated Inflammatory Cytokines in Human Articular Chondrocytes. Nanomaterials 2020, 10, 1238. https://doi.org/10.3390/nano10061238

AMA Style

Urich J, Cucchiarini M, Rey-Rico A. Therapeutic Delivery of rAAV sox9 via Polymeric Micelles Counteracts the Effects of Osteoarthritis-Associated Inflammatory Cytokines in Human Articular Chondrocytes. Nanomaterials. 2020; 10(6):1238. https://doi.org/10.3390/nano10061238

Chicago/Turabian Style

Urich, Jonas, Magali Cucchiarini, and Ana Rey-Rico. 2020. "Therapeutic Delivery of rAAV sox9 via Polymeric Micelles Counteracts the Effects of Osteoarthritis-Associated Inflammatory Cytokines in Human Articular Chondrocytes" Nanomaterials 10, no. 6: 1238. https://doi.org/10.3390/nano10061238

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop