Plasma proteomic profiling of young and old mice reveals cadherin-13 prevents age-related bone loss
- 12 May 2020
- journal article
- research article
- Published by Impact Journals, LLC in Aging
- Vol. 12 (9), 8652-8668
- https://doi.org/10.18632/aging.103184
Abstract
The blood exhibits a dynamic flux of proteins that are secreted by the tissues and cells of the body. To identify novel aging-related circulating proteins, we compared the plasma proteomic profiles of young and old mice using tandem mass spectrometry. The expression of 134 proteins differed between young and old mice. We selected seven proteins that were expressed at higher levels in young mice, and confirmed their plasma expression in immunoassays. The plasma levels of anthrax toxin receptor 2 (ANTXR2), cadherin-13 (CDH-13), scavenger receptor cysteine-rich type 1 protein M130 (CD163), cartilage oligomeric matrix protein (COMP), Dickkopf-related protein 3 (DKK3), periostin, and secretogranin-1 were all confirmed to decrease with age. We then investigated whether any of the secreted proteins influenced bone metabolism and found that CDH-13 inhibited osteoclast differentiation. CDH 13 treatment suppressed the receptor activator of NF-kappa B ligand (RANKL) signaling pathway in bone marrow-derived macrophages, and intraperitoneal administration of CDH-13 delayed age-related bone loss in the femurs of aged mice. These findings suggest that low plasma CDH-13 expression in aged mice promotes aging-associated osteopenia by facilitating excessive osteoclast formation. Thus, CDH-13 could have therapeutic potential as a protein drug for the prevention of osteopenia.Keywords
This publication has 52 references indexed in Scilit:
- Specific factors in blood from young but not old mice directly promote synapse formation and NMDA-receptor recruitmentProceedings of the National Academy of Sciences of the United States of America, 2019
- Quantitative Age-specific Variability of Plasma Proteins in Healthy Neonates, Children and AdultsMolecular & Cellular Proteomics, 2017
- TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and diseaseBone Research, 2016
- Plasma Proteome Profiling to Assess Human Health and DiseaseCell Systems, 2016
- Exposure to a youthful circulation rejuvenates bone repair through modulation of β-cateninNature Communications, 2015
- Genome-Wide Association Scan of Trait DepressionBiological Psychiatry, 2010
- Extending Healthy Life Span—From Yeast to HumansScience, 2010
- A guide and guard: The many faces of T-cadherinCellular Signalling, 2009
- T-cadherin upregulation correlates with cell-cycle progression and promotes proliferation of vascular cellsCardiovascular Research, 2004
- Significance analysis of microarrays applied to the ionizing radiation responseProceedings of the National Academy of Sciences of the United States of America, 2001