CD13 is a critical regulator of cell–cell fusion in osteoclastogenesis

The transmembrane aminopeptidase CD13 is highly expressed in cells of the myeloid lineage, regulates dynamin-dependent receptor endocytosis and recycling and is a necessary component of actin cytoskeletal organization. Here, we show that CD13-deficient mice present a low bone density phenotype with...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2021-05, Vol.11 (1), p.10736-10736, Article 10736
Main Authors: Ghosh, Mallika, Kelava, Tomislav, Madunic, Ivana Vrhovac, Kalajzic, Ivo, Shapiro, Linda H.
Format: Article
Language:English
Subjects:
631/250
631/80
Actin
Aminopeptidase
Apposition
Bone density
Bone growth
Bone marrow
CD13 antigen
Cell fusion
Cytoskeleton
Dynamin
Endocytosis
Genotypes
Humanities and Social Sciences
Localization
Macrophage colony-stimulating factor
multidisciplinary
Osteoclastogenesis
Osteoclasts
Osteogenesis
Phenotypes
Protein turnover
Proteins
Regulatory proteins
Science
Science (multidisciplinary)
TRANCE protein
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The transmembrane aminopeptidase CD13 is highly expressed in cells of the myeloid lineage, regulates dynamin-dependent receptor endocytosis and recycling and is a necessary component of actin cytoskeletal organization. Here, we show that CD13-deficient mice present a low bone density phenotype with increased numbers of osteoclasts per bone surface, but display a normal distribution of osteoclast progenitor populations in the bone marrow and periphery. In addition, the bone formation and mineral apposition rates are similar between genotypes, indicating a defect in osteoclast-specific function in vivo. Lack of CD13 led to exaggerated in vitro osteoclastogenesis as indicated by significantly enhanced fusion of bone marrow-derived multinucleated osteoclasts in the presence of M-CSF and RANKL, resulting in abnormally large cells containing remarkably high numbers of nuclei. Mechanistically, while expression levels of the fusion-regulatory proteins dynamin and DC-STAMP1 must be downregulated for fusion to proceed, these are aberrantly sustained at high levels even in CD13-deficient mature multi-nucleated osteoclasts. Further, the stability of fusion-promoting proteins is maintained in the absence of CD13, implicating CD13 in protein turnover mechanisms. Together, we conclude that CD13 may regulate cell–cell fusion by controlling the expression and localization of key fusion regulatory proteins that are critical for osteoclast fusion.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-90271-x