The Role of Sonic Hedgehog Signaling in Osteoclastogenesis and Jaw Bone Destruction.
Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of its expression appear to correlate with disease progression and metastasis. However, the role of SHH in bone destruction associated with oral squamous cell carcinomas is still unclear. In th...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0151731 |
| _version_ | 1819111996565487616 |
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| author | Tsuyoshi Shimo Kenichi Matsumoto Kiyofumi Takabatake Eriko Aoyama Yuichiro Takebe Soichiro Ibaragi Tatsuo Okui Naito Kurio Hiroyuki Takada Kyoichi Obata Pai Pang Masahiro Iwamoto Hitoshi Nagatsuka Akira Sasaki |
| author_facet | Tsuyoshi Shimo Kenichi Matsumoto Kiyofumi Takabatake Eriko Aoyama Yuichiro Takebe Soichiro Ibaragi Tatsuo Okui Naito Kurio Hiroyuki Takada Kyoichi Obata Pai Pang Masahiro Iwamoto Hitoshi Nagatsuka Akira Sasaki |
| author_sort | Tsuyoshi Shimo |
| collection | DOAJ |
| description | Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of its expression appear to correlate with disease progression and metastasis. However, the role of SHH in bone destruction associated with oral squamous cell carcinomas is still unclear. In this study we analyzed SHH expression and the role played by SHH signaling in gingival carcinoma-induced jawbone destruction. From an analysis of surgically resected lower gingival squamous cell carcinoma mandible samples, we found that SHH was highly expressed in tumor cells that had invaded the bone matrix. On the other hand, the hedgehog receptor Patched and the signaling molecule Gli-2 were highly expressed in the osteoclasts and the progenitor cells. SHH stimulated osteoclast formation and pit formation in the presence of the receptor activator for nuclear factor-κB ligand (RANKL) in CD11b+ mouse bone marrow cells. SHH upregulated phosphorylation of ERK1/2 and p38 MAPK, NFATc1, tartrate-resistant acid phosphatase (TRAP), and Cathepsin K expression in RAW264.7 cells. Our results suggest that tumor-derived SHH stimulated the osteoclast formation and bone resorption in the tumor jawbone microenvironment. |
| first_indexed | 2024-12-22T04:06:29Z |
| format | Article |
| id | doaj.art-f17bdda213e94270ab49870a003f059c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T04:06:29Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f17bdda213e94270ab49870a003f059c2022-12-21T18:39:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01113e015173110.1371/journal.pone.0151731The Role of Sonic Hedgehog Signaling in Osteoclastogenesis and Jaw Bone Destruction.Tsuyoshi ShimoKenichi MatsumotoKiyofumi TakabatakeEriko AoyamaYuichiro TakebeSoichiro IbaragiTatsuo OkuiNaito KurioHiroyuki TakadaKyoichi ObataPai PangMasahiro IwamotoHitoshi NagatsukaAkira SasakiSonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of its expression appear to correlate with disease progression and metastasis. However, the role of SHH in bone destruction associated with oral squamous cell carcinomas is still unclear. In this study we analyzed SHH expression and the role played by SHH signaling in gingival carcinoma-induced jawbone destruction. From an analysis of surgically resected lower gingival squamous cell carcinoma mandible samples, we found that SHH was highly expressed in tumor cells that had invaded the bone matrix. On the other hand, the hedgehog receptor Patched and the signaling molecule Gli-2 were highly expressed in the osteoclasts and the progenitor cells. SHH stimulated osteoclast formation and pit formation in the presence of the receptor activator for nuclear factor-κB ligand (RANKL) in CD11b+ mouse bone marrow cells. SHH upregulated phosphorylation of ERK1/2 and p38 MAPK, NFATc1, tartrate-resistant acid phosphatase (TRAP), and Cathepsin K expression in RAW264.7 cells. Our results suggest that tumor-derived SHH stimulated the osteoclast formation and bone resorption in the tumor jawbone microenvironment.https://doi.org/10.1371/journal.pone.0151731 |
| spellingShingle | Tsuyoshi Shimo Kenichi Matsumoto Kiyofumi Takabatake Eriko Aoyama Yuichiro Takebe Soichiro Ibaragi Tatsuo Okui Naito Kurio Hiroyuki Takada Kyoichi Obata Pai Pang Masahiro Iwamoto Hitoshi Nagatsuka Akira Sasaki The Role of Sonic Hedgehog Signaling in Osteoclastogenesis and Jaw Bone Destruction. PLoS ONE |
| title | The Role of Sonic Hedgehog Signaling in Osteoclastogenesis and Jaw Bone Destruction. |
| title_full | The Role of Sonic Hedgehog Signaling in Osteoclastogenesis and Jaw Bone Destruction. |
| title_fullStr | The Role of Sonic Hedgehog Signaling in Osteoclastogenesis and Jaw Bone Destruction. |
| title_full_unstemmed | The Role of Sonic Hedgehog Signaling in Osteoclastogenesis and Jaw Bone Destruction. |
| title_short | The Role of Sonic Hedgehog Signaling in Osteoclastogenesis and Jaw Bone Destruction. |
| title_sort | role of sonic hedgehog signaling in osteoclastogenesis and jaw bone destruction |
| url | https://doi.org/10.1371/journal.pone.0151731 |
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