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

• Published in: Cellular and molecular life sciences : CMLS Vol. 74; no. 19; pp. 3451 - 3465
• Main Authors: Lolli, Andrea, Penolazzi, Letizia, Narcisi, Roberto, van Osch, Gerjo J. V. M., Piva, Roberta
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.10.2017; Springer Nature B.V
• 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; Gene silencing; RNA interference; MicroRNA; Cartilage repair; Chondrogenesis; Anti-chondrogenic regulators; Mesenchymal stem cells
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-017-2531-z

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.