Protein deubiquitinase USP7 is required for osteogenic differentiation of human adipose-derived stem cells
| Autor: | Wenshu Ge, Yongsheng Zhou, Xiao Zhang, Yong Jiang, Longwei Lv, Wenyue Li, Yiman Tang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cellular differentiation Medicine (miscellaneous) Biochemistry Genetics and Molecular Biology (miscellaneous) Ubiquitin-Specific Peptidase 7 lcsh:Biochemistry 03 medical and health sciences Osteogenesis Osteogenic differentiation Humans lcsh:QD415-436 Progenitor cell Human adipose-derived stem cells Protein deubiquitination Bone engineering Ubiquitin specific protease 7 lcsh:R5-920 Adipogenesis Chemistry Stem Cells Research Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells Cell Biology Molecular biology Deubiquitinase Cell biology Endothelial stem cell 030104 developmental biology Stem cell fate determination Adipose Tissue Indenes Gene Knockdown Techniques Pyrazines Molecular Medicine Stem cell lcsh:Medicine (General) |
| Zdroj: | Stem Cell Research & Therapy, Vol 8, Iss 1, Pp 1-14 (2017) Stem Cell Research & Therapy |
| ISSN: | 1757-6512 |
| DOI: | 10.1186/s13287-017-0637-8 |
| Popis: | Background Human adipose-derived stem cells (hASCs) are multipotent progenitor cells with self-renewal capabilities and multilineage differentiation potential, including osteogenesis. Although protein deubiquitinases have been linked to stem cell fate determination, whether protein deubiquitination contributes to lineage commitment during osteogenic differentiation of hASCs remains to be investigated. The objective of this study was to evaluate the effects of the ubiquitin specific protease 7 (USP7) on osteogenic differentiation of hASCs. Methods An osteocalcin promoter driven luciferase reporter system was established to initially discover the potential association between USP7 and hASC osteogenesis. To further characterize the function of USP7 in osteogenic differentiation of hASCs, a combination of in vitro and in vivo experiments were carried out through genetic depletion or overexpression of USP7 using a lentiviral strategy. Moreover, HBX 41,108, a cyanoindenopyrazine-derived deubiquitinase inhibitor of USP7, was utilized at different doses to further examine whether USP7 regulated osteogenic differentiation of hASCs through its enzymatic activity. Results We demonstrated that USP7 depletion was associated with remarkable downregulation of the reporter gene activity. Genetic depletion of USP7 by lentiviral RNAi markedly suppressed hASC osteogenesis both in vitro and in vivo, while overexpression of USP7 enhanced the osteogenic differentiation of hASCs. Notably, chemical blockade via the small molecular inhibitor HBX 41,108 could efficiently mimic the effects of USP7 genetic depletion in a dose-dependent manner. Conclusions Taken together, our study revealed that protein deubiquitinase USP7 is an essential player in osteogenic differentiation of hASCs through its catalytic activity, and supported the pursuit of USP7 as a potential target for modulation of hASC-based stem cell therapy and bone tissue engineering. Electronic supplementary material The online version of this article (doi:10.1186/s13287-017-0637-8) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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