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Mitf Induction by RANKL Is Critical for Osteoclastogenesis

Microphthalmia-associated transcription factor (Mitf) regulates the development and function of several cell lineages, including osteoclasts. In this report, we identified a novel mechanism by which RANKL regulates osteoclastogenesis via induction of Mitf isoform E (Mitf-E). Both Mitf-A and Mitf-E a...

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Autores principales: Lu, Ssu-Yi, Li, Mengtao, Lin, Yi-Ling
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869381/
https://www.ncbi.nlm.nih.gov/pubmed/20357005
http://dx.doi.org/10.1091/mbc.E09-07-0584
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author Lu, Ssu-Yi
Li, Mengtao
Lin, Yi-Ling
author_facet Lu, Ssu-Yi
Li, Mengtao
Lin, Yi-Ling
author_sort Lu, Ssu-Yi
collection PubMed
description Microphthalmia-associated transcription factor (Mitf) regulates the development and function of several cell lineages, including osteoclasts. In this report, we identified a novel mechanism by which RANKL regulates osteoclastogenesis via induction of Mitf isoform E (Mitf-E). Both Mitf-A and Mitf-E are abundantly present in osteoclasts. Unlike Mitf-A, which is ubiquitously expressed and is present in similar amounts in macrophages and osteoclasts, Mitf-E is almost nondetectable in macrophages, but its expression is significantly up-regulated during osteoclastogenesis. In addition to their different expression profiles, the two isoforms are drastically different in their abilities to support osteoclastogenesis, despite sharing all known functional domains. Unlike Mitf-A, small amounts of Mitf-E are present in nuclear lysates unless chromatin is digested/sheared during the extraction. Based on these data, we propose a model in which Mitf-E is induced during osteoclastogenesis and is closely associated with chromatin to facilitate its interaction with target promoters; therefore, Mitf-E has a stronger osteoclastogenic activity. Mitf-A is a weaker osteoclastogenic factor, but activated Mitf-A alone is not sufficient to fully support osteoclastogenesis. Therefore, this receptor activator for nuclear factor-κB ligand (RANKL)-induced Mitf phenomenon seems to play an important role during osteoclastogenesis. Although the current theory indicates that Mitf and its binding partner Tfe3 are completely redundant in osteoclasts, using RNA interference, we demonstrated that Mitf has a distinct role from Tfe3. This study provides the first evidence that RANKL-induced Mitf is critical for osteoclastogenesis and Mitf is not completely redundant with Tfe3.
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spelling pubmed-28693812010-07-30 Mitf Induction by RANKL Is Critical for Osteoclastogenesis Lu, Ssu-Yi Li, Mengtao Lin, Yi-Ling Mol Biol Cell Articles Microphthalmia-associated transcription factor (Mitf) regulates the development and function of several cell lineages, including osteoclasts. In this report, we identified a novel mechanism by which RANKL regulates osteoclastogenesis via induction of Mitf isoform E (Mitf-E). Both Mitf-A and Mitf-E are abundantly present in osteoclasts. Unlike Mitf-A, which is ubiquitously expressed and is present in similar amounts in macrophages and osteoclasts, Mitf-E is almost nondetectable in macrophages, but its expression is significantly up-regulated during osteoclastogenesis. In addition to their different expression profiles, the two isoforms are drastically different in their abilities to support osteoclastogenesis, despite sharing all known functional domains. Unlike Mitf-A, small amounts of Mitf-E are present in nuclear lysates unless chromatin is digested/sheared during the extraction. Based on these data, we propose a model in which Mitf-E is induced during osteoclastogenesis and is closely associated with chromatin to facilitate its interaction with target promoters; therefore, Mitf-E has a stronger osteoclastogenic activity. Mitf-A is a weaker osteoclastogenic factor, but activated Mitf-A alone is not sufficient to fully support osteoclastogenesis. Therefore, this receptor activator for nuclear factor-κB ligand (RANKL)-induced Mitf phenomenon seems to play an important role during osteoclastogenesis. Although the current theory indicates that Mitf and its binding partner Tfe3 are completely redundant in osteoclasts, using RNA interference, we demonstrated that Mitf has a distinct role from Tfe3. This study provides the first evidence that RANKL-induced Mitf is critical for osteoclastogenesis and Mitf is not completely redundant with Tfe3. The American Society for Cell Biology 2010-05-15 /pmc/articles/PMC2869381/ /pubmed/20357005 http://dx.doi.org/10.1091/mbc.E09-07-0584 Text en © 2010 by The American Society for Cell Biology
spellingShingle Articles
Lu, Ssu-Yi
Li, Mengtao
Lin, Yi-Ling
Mitf Induction by RANKL Is Critical for Osteoclastogenesis
title Mitf Induction by RANKL Is Critical for Osteoclastogenesis
title_full Mitf Induction by RANKL Is Critical for Osteoclastogenesis
title_fullStr Mitf Induction by RANKL Is Critical for Osteoclastogenesis
title_full_unstemmed Mitf Induction by RANKL Is Critical for Osteoclastogenesis
title_short Mitf Induction by RANKL Is Critical for Osteoclastogenesis
title_sort mitf induction by rankl is critical for osteoclastogenesis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869381/
https://www.ncbi.nlm.nih.gov/pubmed/20357005
http://dx.doi.org/10.1091/mbc.E09-07-0584
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