Reciprocal Role of ERK and Nf-κb Pathways in Survival and Activation of Osteoclasts
To examine the role of mitogen-activated protein kinase and nuclear factor kappa B (NF-κB) pathways on osteoclast survival and activation, we constructed adenovirus vectors carrying various mutants of signaling molecules: dominant negative Ras (RasDN), constitutively active MEK1 (MEKCA), dominant ne...
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| Format: | Online |
| Language: | English |
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The Rockefeller University Press
2000
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174281/ |
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pubmed-2174281 |
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pubmed-21742812008-05-01 Reciprocal Role of ERK and Nf-κb Pathways in Survival and Activation of Osteoclasts Miyazaki, Tsuyoshi Katagiri, Hideki Kanegae, Yumi Takayanagi, Hiroshi Sawada, Yasuhiro Yamamoto, Aiichiro Pando, Mattew P. Asano, Tomoichiro Verma, Inder M. Oda, Hiromi Nakamura, Kozo Tanaka, Sakae Original Article To examine the role of mitogen-activated protein kinase and nuclear factor kappa B (NF-κB) pathways on osteoclast survival and activation, we constructed adenovirus vectors carrying various mutants of signaling molecules: dominant negative Ras (RasDN), constitutively active MEK1 (MEKCA), dominant negative IκB kinase 2 (IKKDN), and constitutively active IKK2 (IKKCA). Inhibiting ERK activity by RasDN overexpression rapidly induced the apoptosis of osteoclast-like cells (OCLs) formed in vitro, whereas ERK activation after the introduction of MEKCA remarkably lengthened their survival by preventing spontaneous apoptosis. Neither inhibition nor activation of ERK affected the bone-resorbing activity of OCLs. Inhibition of NF-κB pathway with IKKDN virus suppressed the pit-forming activity of OCLs and NF-κB activation by IKKCA expression upregulated it without affecting their survival. Interleukin 1α (IL-1α) strongly induced ERK activation as well as NF-κB activation. RasDN virus partially inhibited ERK activation, and OCL survival promoted by IL-1α. Inhibiting NF-κB activation by IKKDN virus significantly suppressed the pit-forming activity enhanced by IL-1α. These results indicate that ERK and NF-κB regulate different aspects of osteoclast activation: ERK is responsible for osteoclast survival, whereas NF-κB regulates osteoclast activation for bone resorption. The Rockefeller University Press 2000-01-24 /pmc/articles/PMC2174281/ /pubmed/10648566 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Miyazaki, Tsuyoshi Katagiri, Hideki Kanegae, Yumi Takayanagi, Hiroshi Sawada, Yasuhiro Yamamoto, Aiichiro Pando, Mattew P. Asano, Tomoichiro Verma, Inder M. Oda, Hiromi Nakamura, Kozo Tanaka, Sakae |
| spellingShingle |
Miyazaki, Tsuyoshi Katagiri, Hideki Kanegae, Yumi Takayanagi, Hiroshi Sawada, Yasuhiro Yamamoto, Aiichiro Pando, Mattew P. Asano, Tomoichiro Verma, Inder M. Oda, Hiromi Nakamura, Kozo Tanaka, Sakae Reciprocal Role of ERK and Nf-κb Pathways in Survival and Activation of Osteoclasts |
| author_facet |
Miyazaki, Tsuyoshi Katagiri, Hideki Kanegae, Yumi Takayanagi, Hiroshi Sawada, Yasuhiro Yamamoto, Aiichiro Pando, Mattew P. Asano, Tomoichiro Verma, Inder M. Oda, Hiromi Nakamura, Kozo Tanaka, Sakae |
| author_sort |
Miyazaki, Tsuyoshi |
| title |
Reciprocal Role of ERK and Nf-κb Pathways in Survival and Activation of Osteoclasts |
| title_short |
Reciprocal Role of ERK and Nf-κb Pathways in Survival and Activation of Osteoclasts |
| title_full |
Reciprocal Role of ERK and Nf-κb Pathways in Survival and Activation of Osteoclasts |
| title_fullStr |
Reciprocal Role of ERK and Nf-κb Pathways in Survival and Activation of Osteoclasts |
| title_full_unstemmed |
Reciprocal Role of ERK and Nf-κb Pathways in Survival and Activation of Osteoclasts |
| title_sort |
reciprocal role of erk and nf-κb pathways in survival and activation of osteoclasts |
| description |
To examine the role of mitogen-activated protein kinase and nuclear factor kappa B (NF-κB) pathways on osteoclast survival and activation, we constructed adenovirus vectors carrying various mutants of signaling molecules: dominant negative Ras (RasDN), constitutively active MEK1 (MEKCA), dominant negative IκB kinase 2 (IKKDN), and constitutively active IKK2 (IKKCA). Inhibiting ERK activity by RasDN overexpression rapidly induced the apoptosis of osteoclast-like cells (OCLs) formed in vitro, whereas ERK activation after the introduction of MEKCA remarkably lengthened their survival by preventing spontaneous apoptosis. Neither inhibition nor activation of ERK affected the bone-resorbing activity of OCLs. Inhibition of NF-κB pathway with IKKDN virus suppressed the pit-forming activity of OCLs and NF-κB activation by IKKCA expression upregulated it without affecting their survival. Interleukin 1α (IL-1α) strongly induced ERK activation as well as NF-κB activation. RasDN virus partially inhibited ERK activation, and OCL survival promoted by IL-1α. Inhibiting NF-κB activation by IKKDN virus significantly suppressed the pit-forming activity enhanced by IL-1α. These results indicate that ERK and NF-κB regulate different aspects of osteoclast activation: ERK is responsible for osteoclast survival, whereas NF-κB regulates osteoclast activation for bone resorption. |
| publisher |
The Rockefeller University Press |
| publishDate |
2000 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174281/ |
| _version_ |
1611425554898092032 |