Impaired Fracture Healing Caused by Deficiency of the Immunoreceptor Adaptor Protein DAP12.
Osteoclasts play an important role in bone metabolism, but their exact role in fracture healing remains unclear. DAP12 is an immunoadaptor protein with associated immunoreceptors on myeloid lineage cells, including osteoclasts. Its deficiency causes osteopetrosis due to suppression of osteoclast dev...
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doaj-eb53c3cc03de44e59aa35399f3b6dc892021-03-03T20:03:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01106e012821010.1371/journal.pone.0128210Impaired Fracture Healing Caused by Deficiency of the Immunoreceptor Adaptor Protein DAP12.Masayuki KamimuraYu MoriAkiko Sugahara-TobinaiToshiyuki TakaiEiji ItoiOsteoclasts play an important role in bone metabolism, but their exact role in fracture healing remains unclear. DAP12 is an immunoadaptor protein with associated immunoreceptors on myeloid lineage cells, including osteoclasts. Its deficiency causes osteopetrosis due to suppression of osteoclast development and activation. In this report, we assessed the impact of DAP12 on the fracture healing process using C57BL/6 (B6) and DAP12-/- mice. Healing was evaluated using radiography, micro-CT, histology, immunohistochemistry and real-time RT-PCR. Radiography showed lower callus volume and lower callus radiolucency in DAP12-/- mice during later stages. Micro-CT images and quantitative structural analysis indicated that DAP12-/- mice developed calluses of dense trabecular structures and experienced deteriorated cortical shell formation on the surface. Histologically, DAP12-/- mice showed less cartilaginous resorption and woven bone formation. In addition, prominent cortical shell formation was much less in DAP12-/- mice. Immunohistochemistry revealed lower invasion of F4/80 positive monocytes and macrophages into the fracture hematoma in DAP12-/- mice. The expression levels of Col1a1, Col2a1 and Col10a1 in DAP12-/- mice increased and subsequently became higher than those in B6 mice. There was a decrease in the gene expression of Tnf during the early stages in DAP12-/- mice. Our results indicate that DAP12 deficiency impairs fracture healing, suggesting a significant role of DAP12 in the initial inflammatory response, bone remodeling and regeneration.https://doi.org/10.1371/journal.pone.0128210 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Masayuki Kamimura Yu Mori Akiko Sugahara-Tobinai Toshiyuki Takai Eiji Itoi |
spellingShingle |
Masayuki Kamimura Yu Mori Akiko Sugahara-Tobinai Toshiyuki Takai Eiji Itoi Impaired Fracture Healing Caused by Deficiency of the Immunoreceptor Adaptor Protein DAP12. PLoS ONE |
author_facet |
Masayuki Kamimura Yu Mori Akiko Sugahara-Tobinai Toshiyuki Takai Eiji Itoi |
author_sort |
Masayuki Kamimura |
title |
Impaired Fracture Healing Caused by Deficiency of the Immunoreceptor Adaptor Protein DAP12. |
title_short |
Impaired Fracture Healing Caused by Deficiency of the Immunoreceptor Adaptor Protein DAP12. |
title_full |
Impaired Fracture Healing Caused by Deficiency of the Immunoreceptor Adaptor Protein DAP12. |
title_fullStr |
Impaired Fracture Healing Caused by Deficiency of the Immunoreceptor Adaptor Protein DAP12. |
title_full_unstemmed |
Impaired Fracture Healing Caused by Deficiency of the Immunoreceptor Adaptor Protein DAP12. |
title_sort |
impaired fracture healing caused by deficiency of the immunoreceptor adaptor protein dap12. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
Osteoclasts play an important role in bone metabolism, but their exact role in fracture healing remains unclear. DAP12 is an immunoadaptor protein with associated immunoreceptors on myeloid lineage cells, including osteoclasts. Its deficiency causes osteopetrosis due to suppression of osteoclast development and activation. In this report, we assessed the impact of DAP12 on the fracture healing process using C57BL/6 (B6) and DAP12-/- mice. Healing was evaluated using radiography, micro-CT, histology, immunohistochemistry and real-time RT-PCR. Radiography showed lower callus volume and lower callus radiolucency in DAP12-/- mice during later stages. Micro-CT images and quantitative structural analysis indicated that DAP12-/- mice developed calluses of dense trabecular structures and experienced deteriorated cortical shell formation on the surface. Histologically, DAP12-/- mice showed less cartilaginous resorption and woven bone formation. In addition, prominent cortical shell formation was much less in DAP12-/- mice. Immunohistochemistry revealed lower invasion of F4/80 positive monocytes and macrophages into the fracture hematoma in DAP12-/- mice. The expression levels of Col1a1, Col2a1 and Col10a1 in DAP12-/- mice increased and subsequently became higher than those in B6 mice. There was a decrease in the gene expression of Tnf during the early stages in DAP12-/- mice. Our results indicate that DAP12 deficiency impairs fracture healing, suggesting a significant role of DAP12 in the initial inflammatory response, bone remodeling and regeneration. |
url |
https://doi.org/10.1371/journal.pone.0128210 |
work_keys_str_mv |
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