Please use this identifier to cite or link to this item:
|Title:||Zinc-finger protein 145, acting as an upstream regulator of SOX9, improves the differentiation potential of human mesenchymal stem cells for cartilage regeneration and repair||Authors:||Liu, T.M.
|Issue Date:||Sep-2011||Citation:||Liu, T.M., Guo, X.M., Tan, H.S., Hui, J.H., Lim, B., Lee, E.H. (2011-09). Zinc-finger protein 145, acting as an upstream regulator of SOX9, improves the differentiation potential of human mesenchymal stem cells for cartilage regeneration and repair. Arthritis and Rheumatism 63 (9) : 2711-2720. ScholarBank@NUS Repository. https://doi.org/10.1002/art.30430||Abstract:||Objective Human mesenchymal stem cells (hMSCs) represent one of the most promising stem cell therapies for traumatic injury and age-related degenerative diseases involving cartilage. However, few genetic factors regulating chondrogenesis of MSCs have been identified. One study showed that zinc-finger protein 145 (ZNF145), a transcription factor, was up-regulated during 3-lineage differentiation of hMSCs. The present study was undertaken to validate whether this novel transcription factor is useful for the repair and regeneration of cartilage. Methods Human MSCs were transfected with lentiviral short hairpin RNA (for small interfering RNA knockdown of ZNF145) and a lentiviral vector for overexpression of ZNF145, and the effects of ZNF145 on chondrogenesis were studied using quantitative polymerase chain reaction and immunostaining. Microarray and transient expression analyses were used to determine whether ZNF145 is a factor operating upstream of SOX9. Allogeneic transplantation of hMSCs into osteochondral defects in rats was performed to determine the effects of ZNF145 on repair of cartilage in vivo. Results Small interfering RNA-mediated gene silencing of ZNF145 slowed down chondrogenesis, whereas overexpression of ZNF145 enhanced chondrogenesis. Global gene expression profiling showed up-regulated gene expression in ZNF145-overexpressing MSCs, and transient overexpression of ZNF145 enhanced the expression of SOX9, suggesting that ZNF145 acts as a factor upstream of SOX9, the master regulator of chondrogenesis. Moreover, allogeneic transplantation of hMSCs into osteochondral defects of rat knees showed that ZNF145-overexpressing MSCs repaired cartilage defects better and earlier than empty control MSCs. Conclusion These findings suggest that ZNF145 gene therapy may be a very useful strategy for improving the quality of cartilage regeneration and repair. Copyright © 2011 by the American College of Rheumatology.||Source Title:||Arthritis and Rheumatism||URI:||http://scholarbank.nus.edu.sg/handle/10635/102192||ISSN:||00043591||DOI:||10.1002/art.30430|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Feb 18, 2020
WEB OF SCIENCETM
checked on Feb 11, 2020
checked on Feb 16, 2020
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.