Plasma proteomic profiling of young and old mice reveals cadherin-13 prevents age-related bone loss

Yong Ryoul Yang, Mohammad Humayun Kabir, Jin Hee Park, Jae Il Park, Jae Sook Kang, Shinyeong Ju, Yeo Jin Shin, Seung Min Lee, Jaemin Lee, Seokho Kim, Kwang Pyo Lee, Soo Young Lee, Cheolju Lee, Ki Sun Kwon

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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-κB 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.

Original languageEnglish
Pages (from-to)8652-8668
Number of pages17
JournalAging
Volume12
Issue number9
DOIs
StatePublished - 15 May 2020

Keywords

  • Aging
  • Bone
  • Osteoclast differentiation
  • Plasma proteins
  • Proteomics

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