Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1782181124758306816 |
---|---|
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. |
format | Text |
id | pubmed-2869381 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT lussuyi mitfinductionbyrankliscriticalforosteoclastogenesis AT limengtao mitfinductionbyrankliscriticalforosteoclastogenesis AT linyiling mitfinductionbyrankliscriticalforosteoclastogenesis |