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Research Paper|Volume 13, Issue 1|pp 578—597

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

Tze-Hong Wong1, Ting-Yu Chen2, Kuo-Yun Tseng3, Zih-Ying Chen2, Chung-Hsing Chen4,5, Feng-Huei Lin6,7, Hung-Ming Wu2,8,9, Shankung Lin2,10
  • 1Department of Orthopedics, National Taiwan University Hospital, Hsin-Chu Branch, Taiwan, Republic of China
  • 2Inflammation Research and Drug Development Center, Changhua Christian Hospital, Taiwan, Republic of China
  • 3Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Taiwan, Republic of China
  • 4Institute of Population Health Sciences, National Health Research Institutes, Taiwan, Republic of China
  • 5Taiwan Bioinformatics Institute Core, National Health Research Institutes, Taiwan, Republic of China
  • 6Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taiwan, Republic of China
  • 7Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Taiwan, Republic of China
  • 8Department of Neurology, Changhua Christian Hospital, Taiwan, Republic of China
  • 9Graduate Institute of Acupuncture Science, China Medical University, Taiwan, Republic of China
  • 10Graduate Institute of Biomedical Sciences, China Medical University, Taiwan, Republic of China
* Equal contribution
Received: April 15, 2020Accepted: September 14, 2020Published: November 26, 2020
https://doi.org/10.18632/aging.202166

Copyright: © 2020 Wong et al. 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.

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.