Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jan 26, 2021; 13(1): 128-138
Published online Jan 26, 2021. doi: 10.4252/wjsc.v13.i1.128
Transcriptomic alterations underline aging of osteogenic bone marrow stromal cells
Yu-Hao Cheng, Shu-Fen Liu, Jing-Cheng Dong, Qin Bian
Yu-Hao Cheng, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
Shu-Fen Liu, Institute of Spine, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China
Jing-Cheng Dong, Qin Bian, Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
Author contributions: Liu SF and Bian Q performed the in vivo and ex vivo experiments, respectively; Cheng YH wrote the manuscript and analyzed the data; Dong JC and Bian Q edited the manuscript and provided feedback; Bian Q designed the project.
Supported by the National Natural Science Foundation of China, No. 81573992.
Institutional animal care and use committee statement: The study was approved by the Shanghai Animal Ethics Committee.
Conflict-of-interest statement: Qin Bian is currently a research associate at Johns Hopkins University. The work has been done prior to her entrance to Johns Hopkins University.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Qin Bian, MD, PhD, Professor, Department of Integrative Medicine, Huashan Hospital, Fudan University, Middle Wulumuqi Road, Shanghai 200040, China. bianqin213@126.com
Received: September 1, 2020
Peer-review started: September 1, 2020
First decision: September 15, 2020
Revised: November 1, 2020
Accepted: November 17, 2020
Article in press: November 17, 2020
Published online: January 26, 2021
Processing time: 142 Days and 0.1 Hours
Abstract
BACKGROUND

Multipotent bone marrow stromal cells (BMSCs) are adult stem cells that form functional osteoblasts and play a critical role in bone remodeling. During aging, an increase in bone loss and reduction in structural integrity lead to osteoporosis and result in an increased risk of fracture. We examined age-dependent histological changes in murine vertebrae and uncovered that bone loss begins as early as the age of 1 mo.

AIM

To identify the functional alterations and transcriptomic dynamics of BMSCs during early bone loss.

METHODS

We collected BMSCs from mice at early to middle ages and compared their self-renewal and differentiation potential. Subsequently, we obtained the transcriptomic profiles of BMSCs at 1 mo, 3 mo, and 7 mo.

RESULTS

The colony-forming and osteogenic commitment capacity showed a comparable finding that decreased at the age of 1 mo. The transcriptomic analysis showed the enrichment of osteoblastic regulation genes at 1 mo and loss of osteogenic features at 3 mo. The BMSCs at 7 mo showed enrichment of adipogenic and DNA repair features. Moreover, we demonstrated that the WNT and MAPK signaling pathways were upregulated at 1 mo, followed by increased pro-inflammatory and apoptotic features.

CONCLUSION

Our study uncovered the cellular and molecular dynamics of bone aging in mice and demonstrated the contribution of BMSCs to the early stage of age-related bone loss.

Keywords: Bone marrow stromal cell; Mesenchymal stem cell; Mesenchymal stromal cell; Aging; Bone modeling and remodeling; Transcriptome

Core Tip: Multipotent bone marrow stromal cells (BMSCs) are adult stem cells that form functional osteoblasts and play a critical role in bone remodeling. During aging, an increase in bone loss and reduction in structural integrity lead to osteoporosis and result in an increased risk of fracture. In this study, we examined age-dependent histological changes in murine vertebrae and uncovered that bone loss begins as early as the age of 1 mo. The BMSCs isolated at different ages revealed a consistent decreasing trend in both colony-forming and osteogenic commitment capacity. Moreover, we obtained the transcriptomic profiles of BMSCs at 1 mo, 3 mo, and 7 mo to investigate the distinct molecular and regulatory features that underpin the early loss of osteogenic potential. We showed the enrichment of osteoblastic regulation genes at 1 mo and loss of osteogenic features at 3 mo. The adipogenic and DNA repair features were enriched in the later age at 7 mo. Moreover, we demonstrated that the WNT and MAPK signaling pathways were upregulated at 1 mo, followed by increased pro-inflammatory and apoptotic features.