Journal Article DZNE-2020-06744

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ZNF521 Represses Osteoblastic Differentiation in Human Adipose-Derived Stem Cells.

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2018
Molecular Diversity Preservation International Basel

International journal of molecular sciences 19(12), 4095 () [10.3390/ijms19124095] special issue: "Adipose Stem Cells 2019"

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Abstract: Human adipose-derived stem cells (hADSCs) are multipotent mesenchymal cells that can differentiate into adipocytes, chondrocytes, and osteocytes. During osteoblastogenesis, the osteoprogenitor cells differentiate into mature osteoblasts and synthesize bone matrix components. Zinc finger protein 521 (ZNF521/Zfp521) is a transcription co-factor implicated in the regulation of hematopoietic, neural, and mesenchymal stem cells, where it has been shown to inhibit adipogenic differentiation. The present study is aimed at determining the effects of ZNF521 on the osteoblastic differentiation of hADSCs to clarify whether it can influence their osteogenic commitment. The enforced expression or silencing of ZNF521 in hADSCs was achieved by lentiviral vector transduction. Cells were cultured in a commercial osteogenic medium for up to 20 days. The ZNF521 enforced expression significantly reduced osteoblast development as assessed by the morphological and molecular criteria, resulting in reduced levels of collagen I, alkaline phosphatase, osterix, osteopontin, and calcium deposits. Conversely, ZNF521 silencing, in response to osteoblastic stimuli, induced a significant increase in early molecular markers of osteogenesis and, at later stages, a remarkable enhancement of matrix mineralization. Together with our previous findings, these results show that ZNF521 inhibits both adipocytic and osteoblastic maturation in hADSCs and suggest that its expression may contribute to maintaining the immature properties of hADSCs.

Keyword(s): Adipocytes: cytology (MeSH) ; Adipose Tissue (MeSH) ; Cell Differentiation: genetics (MeSH) ; DNA-Binding Proteins: genetics (MeSH) ; Gene Expression Regulation, Developmental (MeSH) ; Humans (MeSH) ; Mesenchymal Stem Cells: cytology (MeSH) ; Mesenchymal Stem Cells: metabolism (MeSH) ; Multipotent Stem Cells: cytology (MeSH) ; Multipotent Stem Cells: metabolism (MeSH) ; Osteoblasts: cytology (MeSH) ; Osteoblasts: metabolism (MeSH) ; Osteogenesis: genetics (MeSH) ; Stem Cells: cytology (MeSH) ; Stem Cells: metabolism (MeSH) ; DNA-Binding Proteins ; zinc finger protein 521, human

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Contributing Institute(s):
  1. Nuclear Function in CNS Pathophysiology (AG Salomoni)
Research Program(s):
  1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2018
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Medline ; Creative Commons Attribution CC BY (No Version) ; DOAJ ; OpenAccess ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; IF >= 5 ; JCR ; SCOPUS ; Web of Science Core Collection
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 Record created 2020-02-18, last modified 2024-05-01


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