2013 Fiscal Year Final Research Report
The role of Src-p130Cas axis in osteoclastic bone resorption
| Project/Area Number |
24890214
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Functional basic dentistry
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| Research Institution | Saitama Medical University (2013)
Kyushu Dental College (2012) |
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Principal Investigator |
OSAWA Kenji 埼玉医科大学, 医学部, 助教 (70638238)
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| Project Period (FY) |
2012-08-31 – 2014-03-31
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| Keywords | 骨代謝 / 骨吸収 / 破骨細胞 / 細胞内情報伝達 / p130Cas / c-Src / Integrin |
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| Research Abstract |
Osteoclast-specific p130Cas conditional knockout mice (p130Cas cKO) exhibit a high bone mass phenotype caused by defect in multinucleation and cytoskeleton organization causing bone resorption deficiency. Bone marrow cells from p130Cas cKO were able to differentiate into osteoclasts and wild-type cells in vitro. However, osteoclasts from p130Cas cKO failed to form actin rings and resorb pits on dentine slices. Although the initial events of osteoclast attachment were intact, the Rac1 activity that organizes the actin cytoskeleton was reduced, and its distribution was disrupted in p130Cas cKO osteoclasts. Dedicator of cytokinesis 5 (Dock5), a Rho family guanine nucleotide exchanger, failed to associate with Src or Pyk2 in osteoclasts in the absence of p130Cas. These results strongly indicate that p130Cas plays pivotal roles in osteoclastic bone resorption
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[Journal Article] RelB-induced expression of Cot, an MAP3K family member, rescues RANKL-induced osteoclastogenesis in alymphoplasia mice by promoting NF-κB2 processing by IKKα2014
Author(s)
Taniguchi R, Fukushima H, Osawa K, Maruyama T, Yasuda H, Weih F, Doi T, Maki K, Jimi E
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Journal Title
J Biol Chem
Volume: 289(11)
Pages: 7349-61
DOI
Peer Reviewed
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[Journal Article] p130Cas, Crk-associated substrate, plays important roles in osteoclastic bone resorption2013
Author(s)
Nagai Y, Osawa K, Fukushima H, Tamura Y, Aoki K, Ohya K, Yasuda H, Hikiji H, Takahashi M, Seta Y, Seo S, Kurokawa M, Kato S, Honda H, Nakamura I, Maki K, Jimi E
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J Bone Miner Res
Volume: 28(12)
Pages: 2449-62
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[Journal Article] Disruption of NF-κB1 prevents bone loss caused by mechanical unloading2013
Author(s)
Nakamura H, Aoki K, Masuda W, Alles N, Nagano K, Fukushima H, Osawa K, Yasuda H, Nakamura I, Mikuni-Takagaki Y, Ohya K, Maki K, Jimi E
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Journal Title
J Bone Miner Res
Volume: 28(6)
Pages: 1457-67
DOI
Peer Reviewed
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