Spi-C positively regulates RANKL-mediated osteoclast differentiation and function

Eun Mi Go, Ju Hee Oh, Jin Hee Park, Soo Young Lee, Na Kyung Lee

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6 Scopus citations


Spi-C is an SPI-group erythroblast transformation-specific domain transcription factor expressed during B-cell development. Here, we report that Spi-C is a novel receptor activator of nuclear factor-κB ligand (RANKL)-inducible protein that positively regulates RANKL-mediated osteoclast differentiation and function. Knockdown of Spi-C decreased the expression of RANKL-induced nuclear factor of activated T-cells, cytoplasmic 1, receptor activator of nuclear factor-κB (RANK), and tartrate-resistant acid phosphatase (TRAP), resulting in a marked decrease in the number of TRAP-positive multinucleated cells. Spi-C-transduced bone marrow-derived monocytes/macrophages (BMMs) displayed a significant increase in osteoclast formation in the presence of RANKL. In addition, Spi-C-depleted cells failed to show actin ring formation or bone resorption owing to a marked reduction in the expression of RANKL-mediated dendritic cell-specific transmembrane protein and the d2 isoform of vacuolar (H+) ATPase V0 domain, which are known osteoclast fusion-related genes. Interestingly, RANKL stimulation induced the translocation of Spi-C from the cytoplasm into the nucleus during osteoclastogenesis, which was specifically blocked by inhibitors of p38 mitogen-activated protein kinase (MAPK) or PI3 kinase. Moreover, Spi-C depletion prevented RANKL-induced MAPK activation and the degradation of inhibitor of κB-α (IκBα) in BMMs. Collectively, these results suggest that Spi-C is a novel positive regulator that promotes both osteoclast differentiation and function.

Original languageEnglish
Pages (from-to)691-701
Number of pages11
JournalExperimental and Molecular Medicine
Issue number4
StatePublished - 1 Apr 2020

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea (2016R1D1A1B01012205 to N.K.L., and 2019R1A5A6099645 and 2019R1A6C1010020 to S.Y.L.) and the Soonchunhyang University Research Fund.

Publisher Copyright:
© 2020, The Author(s).


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