TY - JOUR
T1 - The role of sonic hedgehog signaling in osteoclastogenesis and jaw bone destruction
AU - Shimo, Tsuyoshi
AU - Matsumoto, Kenichi
AU - Takabatake, Kiyofumi
AU - Aoyama, Eriko
AU - Takebe, Yuichiro
AU - Ibaragi, Soichiro
AU - Okui, Tatsuo
AU - Kurio, Naito
AU - Takada, Hiroyuki
AU - Obata, Kyoichi
AU - Pang, Pai
AU - Iwamoto, Masahiro
AU - Nagatsuka, Hitoshi
AU - Sasaki, Akira
N1 - Funding Information:
We thank Drs. Motomi Enomoto Iwamoto and Takahito Yuasa for their useful input. This work was partly supported by a Grant-in-Aid for Young Scientists (A) (to T.S.) and a Grant-in-Aid for Scientific Research (B) (to T.S.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
Publisher Copyright:
© 2016 Shimo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/3
Y1 - 2016/3
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0151731
DO - 10.1371/journal.pone.0151731
M3 - Article
C2 - 27007126
AN - SCOPUS:84962056799
SN - 1932-6203
VL - 11
JO - PLoS One
JF - PLoS One
IS - 3
M1 - e0151731
ER -
