CD13 is a critical regulator of cell–cell fusion in osteoclastogenesis (CROSBI ID 294952)
Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija
Podaci o odgovornosti
Ghosh, Mallika ; Kelava, Tomislav ; Vrhovac Madunić, Ivana ; Kalajzić, Ivo ; Shapiro, Linda H.
engleski
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-defcient 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-specifc function in vivo. Lack of CD13 led to exaggerated in vitro osteoclastogenesis as indicated by signifcantly 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- defcient 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.
osteoclasts ; mineral apposition rate ; CD13KO ; TRAP ; RANKL
nije evidentirano
nije evidentirano
nije evidentirano
nije evidentirano
nije evidentirano
nije evidentirano
Podaci o izdanju
Povezanost rada
Biologija, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje), Temeljne medicinske znanosti