Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Dec 21:12:610581.
doi: 10.3389/fnagi.2020.610581. eCollection 2020.

Regulatory Roles of Bone in Neurodegenerative Diseases

Zhengran Yu  1 , Zemin Ling  1 , Lin Lu  2 , Jin Zhao  2 , Xiang Chen  2 , Pingyi Xu  2 , Xuenong Zou  1
Affiliations
Review

Regulatory Roles of Bone in Neurodegenerative Diseases

Zhengran Yu et al. Front Aging Neurosci. .

Abstract

Osteoporosis and neurodegenerative diseases are two kinds of common disorders of the elderly, which often co-occur. Previous studies have shown the skeletal and central nervous systems are closely related to pathophysiology. As the main structural scaffold of the body, the bone is also a reservoir for stem cells, a primary lymphoid organ, and an important endocrine organ. It can interact with the brain through various bone-derived cells, mostly the mesenchymal and hematopoietic stem cells (HSCs). The bone marrow is also a place for generating immune cells, which could greatly influence brain functions. Finally, the proteins secreted by bones (osteokines) also play important roles in the growth and function of the brain. This article reviews the latest research studying the impact of bone-derived cells, bone-controlled immune system, and bone-secreted proteins on the brain, and evaluates how these factors are implicated in the progress of neurodegenerative diseases and their potential use in the diagnosis and treatment of these diseases.

Keywords: bone; bone marrow; immune; mesenchymal stem cells; neurodegenerative diseases; osteokines.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Bone marrow-derived cells influence the brain. BM-MSC, bone marrow mesenchymal stem cell; HSC, hematopoietic stem cell.
Figure 2
Figure 2
The detrimental and beneficial roles of different immune cells in neurodegenerative diseases. With the aging bone marrow, pro-inflammatory lymphocytes (CTL, Th1, Th17) are activated, while immunomodulatory lymphocytes (Th2, Tregs) are suppressed, thus promoting the progression of neurodegenerative diseases. AD, Alzheimer’s disease; BBB, blood-brain barrier; CTL, cytotoxic T lymphocyte; IFN-γ, interferon-γ; MS, multiple sclerosis; PD, Parkinson disease; SN, substantia nigra; TNF-α, tumor necrosis factor-α.
See this image and copyright information in PMC

References

    1. Afzali B., Mitchell P., Lechler R. I., John S., Lombardi G. (2010). Translational mini-review series on Th17 cells: induction of interleukin-17 production by regulatory T cells. Clin. Exp. Immunol. 159, 120–130. 10.1111/j.1365-2249.2009.04038.x - DOI - PMC - PubMed
    1. Ahmed S., Mahmood Z., Javed A., Hashmi S. N., Zerr I., Zafar S., et al. . (2017). Effect of metformin on adult hippocampal neurogenesis: comparison with donepezil and links to cognition. J. Mol. Neurosci. 62, 88–98. 10.1007/s12031-017-0915-z - DOI - PubMed
    1. Ajami B., Bennett J. L., Krieger C., Tetzlaff W., Rossi F. M. (2007). Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat. Neurosci. 10, 1538–1543. 10.1038/nn2014 - DOI - PubMed
    1. Al Nimer F., Elliott C., Bergman J., Khademi M., Dring A. M., Aeinehband S., et al. . (2016). Lipocalin-2 is increased in progressive multiple sclerosis and inhibits remyelination. Neurol. Neuroimmunol. Neuroinflamm. 3:e191. 10.1212/NXI.0000000000000191 - DOI - PMC - PubMed
    1. Alvarez-Erviti L., Seow Y., Yin H., Betts C., Lakhal S., Wood M. J. (2011). Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol. 29, 341–345. 10.1038/nbt.1807 - DOI - PubMed