Emerging potential of gene silencing approaches targeting anti-chondrogenic factors for cell-based cartilage repair

The field of cartilage repair has exponentially been growing over the past decade. Here, we discuss the possibility to achieve satisfactory regeneration of articular cartilage by means of human mesenchymal stem cells (hMSCs) depleted of anti-chondrogenic factors and implanted in the site of injury....

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Bibliographic Details
Published in:Cellular and molecular life sciences : CMLS 2017-10, Vol.74 (19), p.3451-3465
Main Authors: Lolli, Andrea, Penolazzi, Letizia, Narcisi, Roberto, van Osch, Gerjo J. V. M., Piva, Roberta
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cartilage
Cartilage, Articular - injuries
Cartilage, Articular - physiology
Cell Biology
Cells
Chondrocytes
Chondrogenesis
DNA repair
Gene expression
Genes
Humans
Life Sciences
Mesenchymal Stem Cell Transplantation - methods
Mesenchymal stem cells
Mesenchymal Stem Cells - metabolism
Modulators
Optimization
Regeneration
Regulators
Repair
Review
RNA Interference
RNA, Small Interfering - administration & dosage
RNA, Small Interfering - genetics
RNA, Small Interfering - therapeutic use
RNA, Untranslated - genetics
RNAi Therapeutics - methods
Stem cells
Tissues
Transcription Factors - genetics
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Summary:The field of cartilage repair has exponentially been growing over the past decade. Here, we discuss the possibility to achieve satisfactory regeneration of articular cartilage by means of human mesenchymal stem cells (hMSCs) depleted of anti-chondrogenic factors and implanted in the site of injury. Different types of molecules including transcription factors, transcriptional co-regulators, secreted proteins, and microRNAs have recently been identified as negative modulators of chondroprogenitor differentiation and chondrocyte function. We review the current knowledge about these molecules as potential targets for gene knockdown strategies using RNA interference (RNAi) tools that allow the specific suppression of gene function. The critical issues regarding the optimization of the gene silencing approach as well as the delivery strategies are discussed. We anticipate that further development of these techniques will lead to the generation of implantable hMSCs with enhanced potential to regenerate articular cartilage damaged by injury, disease, or aging.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-017-2531-z