NDLI: Decorin inhibits the insulin-like growth factor I signaling in bone marrow mesenchymal stem cells of aged humans.

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Decorin inhibits the insulin-like growth factor I signaling in bone marrow mesenchymal stem cells of aged humans.

Content Provider	Europe PMC
Author	Wong, Tze-Hong Chen, Ting-Yu Tseng, Kuo-Yun Chen, Zih-Ying Chen, Chung-Hsing Lin, Feng-Huei Wu, Hung-Ming Lin, Shankung
Abstract	Aging impairs the IGF-I signaling of bone marrow mesenchymal stem cells (bmMSCs), but the mechanism is unclear. Here, we found that the ability to auto-phosphorylate IGF-I receptor (IGF-IR) in response to IGF-I was decreased in the bmMSCs of aged donors. Conversely, data showed that decorin (DCN) expression was prominently increased in aged bmMSCs, and that under IGF-I treatment, DCN knockdown in serum-starved aged bmMSCs potentiated their mitogenic activity and IGF-IR auto-phosphorylation, whereas DCN overexpression in serum-starved adult bmMSCs decreased both activities. Co-immunoprecipitation assays suggested that IGF-I and DCN bound to IGF-IR in a competitive manner. Online MethPrimer predicted 4 CpG islands (CGIs) in the introns of DCN gene. RT-qPCR and bisulfite sequencing showed that dimethyloxalylglycine, an inhibitor of DNA demethylation, increased DCN mRNA expression and CGI-I methylation in adult bmMSCs, whereas 5-aza-2’-deoxycytidine, a DNA methylation inhibitor, decreased DCN mRNA expression and CGI-I methylation in aged bmMSCs, and ultimately enhanced the proliferation of serum-starved aged bmMSCs under IGF-I stimulation. Thus, IGF-IR could be the prime target of aging in down-regulating the IGF-I signaling of bmMSCs, where DCN could be a critical mediator.
Journal	Aging
Volume Number	13
PubMed Central reference number	PMC7835024
Issue Number	1
PubMed reference number	33257596
e-ISSN	19454589
DOI	10.18632/aging.202166
Language	English
Publisher	Impact Journals
Publisher Date	2020-11-26
Access Restriction	Open
Rights License	This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: © 2020 Wong et al.
Subject Keyword	aging osteoporosis IGF-I small leucine-rich proteoglycan bone marrow mesenchymal stem cell
Content Type	Text
Resource Type	Article
Subject	Aging Cell Biology

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