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Int. J. Mol. Sci. 2017, 18(9), 1842; doi:10.3390/ijms18091842

RNA Interference and BMP-2 Stimulation Allows Equine Chondrocytes Redifferentiation in 3D-Hypoxia Cell Culture Model: Application for Matrix-Induced Autologous Chondrocyte Implantation

1
Normandie Université, UNICAEN, Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT), équipe Microenvironnement des Pathologies Dégénératives et Fibrotiques (MIPDF), EA 4652/BIOTARGEN EA 7450, UFR Santé, Université de Caen Normandie, 14032 Caen, France
2
Vetbiobank, 1 Avenue Bourgelat, 69280 Marcy l’Etoile, France
3
Imaging and Research Centre of Equine Locomotor Disorders (CIRALE, 14430 Goustranville, France), Ecole Nationale Vétérinaire d’Alfort, 94704 Maisons-Alfort, France
*
Author to whom correspondence should be addressed.
Received: 20 July 2017 / Revised: 18 August 2017 / Accepted: 22 August 2017 / Published: 24 August 2017
(This article belongs to the Special Issue Musculoskeletal Diseases Therapy)
View Full-Text   |   Download PDF [8830 KB, uploaded 24 August 2017]   |  

Abstract

As in humans, osteoarthritis (OA) causes considerable economic loss to the equine industry. New hopes for cartilage repair have emerged with the matrix-associated autologous chondrocyte implantation (MACI). Nevertheless, its limitation is due to the dedifferentiation occurring during the chondrocyte amplification phase, leading to the loss of its capacity to produce a hyaline extracellular matrix (ECM). To enhance the MACI therapy efficiency, we have developed a strategy for chondrocyte redifferentiation, and demonstrated its feasibility in the equine model. Thus, to mimic the cartilage microenvironment, the equine dedifferentiated chondrocytes were cultured in type I/III collagen sponges for 7 days under hypoxia in the presence of BMP-2. In addition, chondrocytes were transfected by siRNA targeting Col1a1 and Htra1 mRNAs, which are overexpressed during dedifferentiation and OA. To investigate the quality of the neo-synthesized ECM, specific and atypical cartilage markers were evaluated by RT-qPCR and Western blot. Our results show that the combination of 3D hypoxia cell culture, BMP-2 (Bone morphogenetic protein-2), and RNA interference, increases the chondrocytes functional indexes (Col2a1/Col1a1, Acan/Col1a1), leading to an effective chondrocyte redifferentiation. These data represent a proof of concept for this process of application, in vitro, in the equine model, and will lead to the improvement of the MACI efficiency for cartilage tissue engineering therapy in preclinical/clinical trials, both in equine and human medicine. View Full-Text
Keywords: chondrocyte; tissue engineering; equine model; dedifferentiation; matrix-associated autologous chondrocyte implantation (MACI); BMP-2; hypoxia; siRNA; Col1a1; HtrA1; type II collagen chondrocyte; tissue engineering; equine model; dedifferentiation; matrix-associated autologous chondrocyte implantation (MACI); BMP-2; hypoxia; siRNA; Col1a1; HtrA1; type II collagen
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Rakic, R.; Bourdon, B.; Hervieu, M.; Branly, T.; Legendre, F.; Saulnier, N.; Audigié, F.; Maddens, S.; Demoor, M.; Galera, P. RNA Interference and BMP-2 Stimulation Allows Equine Chondrocytes Redifferentiation in 3D-Hypoxia Cell Culture Model: Application for Matrix-Induced Autologous Chondrocyte Implantation. Int. J. Mol. Sci. 2017, 18, 1842.

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