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Pregled bibliografske jedinice broj: 1128778

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


Ghosh, Mallika; Kelava, Tomislav; Vrhovac Madunic, Ivana; Kalajzic, Ivo; Shapiro, Linda H.
CD13 is a critical regulator of cell–cell fusion in osteoclastogenesis // Scientific reports, 11 (2021), 10736, 1 doi:10.1038/s41598-021-90271-x (međunarodna recenzija, članak, znanstveni)


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

Autori
Ghosh, Mallika ; Kelava, Tomislav ; Vrhovac Madunic, Ivana ; Kalajzic, Ivo ; Shapiro, Linda H.

Izvornik
Scientific reports (2045-2322) 11 (2021); 10736, 1

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
osteoclasts, mineral apposition rate, CD13KO, TRAP, RANKL

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)



POVEZANOST RADA


Ustanove:
Institut za medicinska istraživanja i medicinu rada, Zagreb

Poveznice na cjeloviti tekst rada:

doi www.nature.com www.nature.com

Citiraj ovu publikaciju:

Ghosh, Mallika; Kelava, Tomislav; Vrhovac Madunic, Ivana; Kalajzic, Ivo; Shapiro, Linda H.
CD13 is a critical regulator of cell–cell fusion in osteoclastogenesis // Scientific reports, 11 (2021), 10736, 1 doi:10.1038/s41598-021-90271-x (međunarodna recenzija, članak, znanstveni)
Ghosh, M., Kelava, T., Vrhovac Madunic, I., Kalajzic, I. & Shapiro, L. (2021) CD13 is a critical regulator of cell–cell fusion in osteoclastogenesis. Scientific reports, 11, 10736, 1 doi:10.1038/s41598-021-90271-x.
@article{article, author = {Ghosh, Mallika and Kelava, Tomislav and Vrhovac Madunic, Ivana and Kalajzic, Ivo and Shapiro, Linda H.}, year = {2021}, pages = {1}, DOI = {10.1038/s41598-021-90271-x}, chapter = {10736}, keywords = {osteoclasts, mineral apposition rate, CD13KO, TRAP, RANKL}, journal = {Scientific reports}, doi = {10.1038/s41598-021-90271-x}, volume = {11}, issn = {2045-2322}, title = {CD13 is a critical regulator of cell–cell fusion in osteoclastogenesis}, keyword = {osteoclasts, mineral apposition rate, CD13KO, TRAP, RANKL}, chapternumber = {10736} }
@article{article, author = {Ghosh, Mallika and Kelava, Tomislav and Vrhovac Madunic, Ivana and Kalajzic, Ivo and Shapiro, Linda H.}, year = {2021}, pages = {1}, DOI = {10.1038/s41598-021-90271-x}, chapter = {10736}, keywords = {osteoclasts, mineral apposition rate, CD13KO, TRAP, RANKL}, journal = {Scientific reports}, doi = {10.1038/s41598-021-90271-x}, volume = {11}, issn = {2045-2322}, title = {CD13 is a critical regulator of cell–cell fusion in osteoclastogenesis}, keyword = {osteoclasts, mineral apposition rate, CD13KO, TRAP, RANKL}, chapternumber = {10736} }

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