title: Zinc finger factor 521 enhances adipogenic differentiation of mouse multipotent cells and human bone marrow mesenchymal stem cells.
abstract: Previously, we found that ZNF521 expression was up-regulated with advancing age in human bone marrow mesenchymal stem cells (bmMSCs). Here, we investigated the regulatory role of ZNF521 in the differentiation of mouse C3H10T1/2 cells and human bmMSCs. Our data show that ZNF521 overexpression repressed osteoblastic differentiation of C3H10T1/2 cells, accompanied by a decrease in Runx2 expression and an increase in PPARγ2 expression. In contrast, ZNF521 overexpression enhanced adipogenic differentiation of C3H10T1/2 cells, concomitant with increased expression of PPARγ2, aP2, adiponectin and C/EBPδ. Chromatin immunoprecipitation followed by quantitative PCR analyses and luciferase reporter assays suggested that ZNF521 overexpression enhances PPARγ2 expression at the transcriptional level. The enhancing effect of ZNF521 overexpression on the adipogenic differentiation of C3H10T1/2 cells was also observed ex vivo. Finally, similar to those noted in C3H10T1/2 cells, ZNF521 overexpression in human bmMSCs was found to promote adipogenic differentiation in vitro and ex vivo, but repressed osteoblastic differentiation in vitro. ZNF521 knockdown significantly repressed adipogenic differentiation in vitro and ex vivo, but promoted osteoblastic differentiation in vitro. We propose that ZNF521 can function as a repressor of osteoblastic differentiation of bmMSCs while promoting adipogenesis, and that elevated ZNF521 expression might play a role in the age-related bone loss.
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan, Republic of China.
authors.forename: Kuo-Yun
authors.initials: KY
authors.lastname: Tseng
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan, Republic of China.|Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, Republic of China.
authors.forename: Shankung
authors.initials: S
authors.lastname: Lin
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008809:Mice, Inbred C3H; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C472572:Evi3 protein, mouse; D047495:PPAR gamma; D014157:Transcription Factors; C529598:zinc finger protein 521, human
keywords: Gerotarget; adipogenesis; age-related bone loss; aging; marrow MSC; osteoporosis