Lentivirus-mediated knockdown of aggrecanase-1 and -2 promotes chondrocyte-engineered cartilage formation in vitro

Biotechnology and Bioengineering
Zheng-hui WangZhe Xing

Abstract

Chondrocyte-based tissue engineering has emerged as a promising approach for repair of injured cartilage tissues that have a poor self-healing capacity. However, this technique faces a major limitation: dedifferentiation of chondrocytes occurs following several passages in culture. Aggrecan, a major component of cartilage extracellular matrix, plays an essential role in chondrocyte differentiation. The aim of this study is to determine whether inhibition of chondrocyte aggrecanases, key degradative enzymes for aggrecan in cartilage, could benefit chondrocyte differentiation and the preservation of chondrocyte phenotype within a long-term period. Lentivirus-mediated RNA interference (RNAi) was employed to target both aggrecanase-1 and -2 in primary rat chondrocytes, and the transduced cells were seeded into chitosan-gelatin three-dimensional scaffolds. Histological, morphological, and biochemical analyses were performed at 1-8 weeks post-implantation to study chondrocyte survival, differentiation, and function. We found that lentivirus-mediated RNAi notably decreased the abundance of aggrecanase transcripts in chondrocytes but did not affect cell viability. Most importantly, compared to the control constructs seeded with untrans...Continue Reading

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Oct 6, 2012·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Jing DuYan Cai
Apr 10, 2014·Tissue Engineering. Part a·Gina LisignoliRoberta Piva
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Feb 19, 2019·Bioorganic & Medicinal Chemistry·Xiao-Yu YuanSaida Mebarek

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