About: CD13 is a Critical Regulator of Cell-cell Fusion in Osteoclastogenesis

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	CD13 is a Critical Regulator of Cell-cell Fusion in Osteoclastogenesis
Creator	Ghosh, Mallika Shapiro, Linda Aguila, Hector Kalajzic, Ivo
Source	BioRxiv
abstract	In vertebrates, bone formation is dynamically controlled by the activity of two specialized cell types: the bone-generating osteoblasts and bone-degrading osteoclasts. Osteoblasts produce the soluble receptor activator of NFκB ligand (RANKL) that binds to its receptor RANK on the surface of osteoclast precursor cells to promote osteoclastogenesis, a process that involves cell-cell fusion and assembly of molecular machinery to ultimately degrade the bone. CD13 is a transmembrane aminopeptidase that is highly expressed in cells of myeloid lineage has been shown to regulate dynamin-dependent receptor endocytosis and recycling and is a necessary component of actin cytoskeletal organization. In the present study, we show that CD13-deficient mice display a normal distribution of osteoclast progenitor populations in the bone marrow, but present a low bone density phenotype. Further, the endosteal bone formation rate is similar between genotypes, indicating a defect in osteoclast-specific function in vivo. Loss 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 with remarkably high numbers of nuclei with a concomitant increase in bone resorption activity. Similarly, we also observed increased formation of multinucleated giant cells (MGC) in CD13KO bone marrow progenitor cells stimulated with IL-4 and IL-13, suggesting that CD13 may regulate cell-cell fusion events via a common pathway, independent of RANKL signaling. Mechanistically, while expression levels of the fusion-regulatory proteins dynamin and DC-STAMP are normally downregulated as fusion progresses in fusion-competent mononucleated progenitor cells, in the absence of CD13 they are uniformly sustained at high levels, even in mature multi-nucleated osteoclasts. Taken together, we conclude that CD13 may regulate cell-cell fusion by controlling expression and localization of key fusion proteins that are critical for both osteoclast and MGC fusion.
has issue date	2020-06-30(xsd:dateTime)
bibo:doi	10.1101/2020.04.25.061325
has license	biorxiv
sha1sum (hex)	ca8adbb5ef914bd0055be7c768e90ab4e077b6a2
schema:url	https://doi.org/10.1101/2020.04.25.061325
resource representing a document's title	CD13 is a Critical Regulator of Cell-cell Fusion in Osteoclastogenesis
schema:publication	bioRxiv
resource representing a document's body	covid:ca8adbb5ef914bd0055be7c768e90ab4e077b6a2#body_text
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