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Targeting aging with the healthy skeletal system: The endocrine role of bone

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Abstract

Aging is an inevitable biological process, and longevity may be related to bone health. Maintaining strong bone health can extend one’s lifespan, but the exact mechanism is unclear. Bone and extraosseous organs, including the heart and brain, have complex and precise communication mechanisms. In addition to its load bearing capacity, the skeletal system secretes cytokines, which play a role in bone regulation of extraosseous organs. FGF23, OCN, and LCN2 are three representative bone-derived cytokines involved in energy metabolism, endocrine homeostasis and systemic chronic inflammation levels. Today, advanced research methods provide new understandings of bone as a crucial endocrine organ. For example, gene editing technology enables bone-specific conditional gene knockout models, which allows the study of bone-derived cytokines to be more precise. We systematically evaluated the various effects of bone-derived cytokines on extraosseous organs and their possible antiaging mechanism. Targeting aging with the current knowledge of the healthy skeletal system is a potential therapeutic strategy. Therefore, we present a comprehensive review that summarizes the current knowledge and provides insights for futures studies.

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Abbreviations

Adeno-Associated Virus:

AAV

Adenosine 5‘-Monophosphate (AMP)-Activated Protein Kinase:

AMPK

Alzheimer'sDisease:

AD

Autosomal Dominant Hypophosphatemic Rickets:

ADHR

Blood-Brain Barrier:

BBB

Bone Mineral Density:

BMD

Bone Morphogenetic Protein:

BMP

Brain-Derived Neurotrophic Factor:

BDNF

Chondrocyte:

CH

Chronic Obstructive Pulmonary Disease:

COPD

Dentin Matrix Protein 1:

DMP1

Fibroblast Growth Factor 23:

FGF23

GrowthDifferentiation Factor-11:

GDF11

Grancalcin:

GCA

Homeobox A3:

HOXA3

Hypoxia-Inducible Factor 1Α:

HIF-1Α

Insulin-Like Growth Factor 1:

IGF 1

Interleukin-6:

IL-6

Lipocalin-2:

LCN2

Long-Term Potentiation:

LTP

Macrophage Colony Stimulating Factor:

M-CSF

Melanocorticoid 4 Receptor:

MC4R

Mouse Vascular Smooth Muscle Cells:

MOVAS

Neuromuscular Junctions:

Nmjs

Nuclear Factor:

NFAT

Nucleotide- Binding Oligomerization Domain, Leucine- Rich Repeat And Pyrin Domain-Containing 3:

NLRP3

Oligodendrocyte:

OL

Osteoblast:

OB

Osteocalcin:

OCN

Osteopontin:

OPN

Osteoprotegerin:

OPG

Parathyroid Hormone:

PTH

Parkinson'sDisease:

PD

Peripheral Blood Mononuclear Cells:

Pbmcs

Phosphate-Regulating Endopeptidase Homolog:

X-Linked, PHEX

Phospholipase CΓ:

PLCΓ

Platelet-Derived Growth Factor Subunit B:

PDGF-BB

Receptor Activator For Nuclear Factor-Κ B Ligand:

RANKL

Reticulocalbin-2:

RCN2

TransformingGrowth Factor:

TGF

Vascular Endothlial Growth Factor:

VEGF

Wnt Family Member 10B:

WNT10B

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Acknowledgments

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. All authors report there are no conflicts of interest related to the present article.

Funding

This work was supported by the National Key Research and Development Program (2020YFC2009004, 2021YFC2501700), the National Natural Science Foundation of China (81874010, 82272554) and PKU-Baidu Fund (2020BD014).

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  1. Department of Orthopaedics, Peking University Third Hospital, Beijing, China

    Xuan-Qi Zheng, Jia-Liang Lin, Jie Huang, Tong Wu & Chun-Li Song

  2. Beijing Key Laboratory of Spinal Disease Research, Beijing, China

    Chun-Li Song

  3. Engineering Research Center of Bone and Joint Precision Medicine, Beijing, China

    Chun-Li Song

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Zheng contributed as first authors. Zheng, Song had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Zheng, Song. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Zheng, Song. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Zheng, Song. Obtained funding: Song. Administrative, technical, or material support: Song. Supervision: Song.

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Zheng, XQ., Lin, JL., Huang, J. et al. Targeting aging with the healthy skeletal system: The endocrine role of bone. Rev Endocr Metab Disord 24, 695–711 (2023). https://doi.org/10.1007/s11154-023-09812-6

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