Molecul ar epidemiological study of the regulation of bone and joint destruction through intracellular ATP and ROS levels
Project/Area Number |
21591965
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Orthopaedic surgery
|
Research Institution | Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology |
Principal Investigator |
MIYAZAKI Tsuyoshi 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (50376480)
|
Co-Investigator(Kenkyū-buntansha) |
MIYAMOTO Yoshinari 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (10345217)
TANAKA Sakae 東京大学, 医学部・附属病院整形外科, 教授 (50282661)
|
Project Period (FY) |
2009 – 2011
|
Project Status |
Completed (Fiscal Year 2011)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 骨関節破壊 / 破骨細胞 / ミトコンドリア / ミトコンドリア転写因子A / 骨吸収 / 関節リウマチ / スーパーオキシドディスムターゼ |
Research Abstract |
Osteoclasts have two conflicting tendencies : lower capacity to survive and higher capacity to execute energy-consuming activities like bone resorption. Here, we report that mature mitochondria-rich osteoclasts have lower intracellular ATP compared to their precursors. Severe ATP depletion caused by disrupting the gene of mitochondrial transcription factor A(Tfam) leads to increased bone-resorbing activity despite accelerated apoptosis. The release of ATP from intracellular stores negatively regulates bone-resorbing activity through an autocrine/paracrine feedback loop by altering cytoskeletal structures. Thus, our study provides evidence for a mechanism by reciprocal changes in intracellular and extracellular ATP, which regulate the negative correlation between osteoclast survival and bone resorption.
|
Report
(4 results)
Research Products
(39 results)
-
[Journal Article] 3,4-Diaminopyridine improves neuromuscular transmission in a MuSK antibody-induced mouse model of myasthenia gravis2012
Author(s)
Mori, S. , Kishi, M., Kubo, S., Akiyoshi, T., Yamada, S., Miyazaki, T., Konishi, T., Maruyama, N., and Shigemoto, K.
-
Journal Title
Journal of neuroimmunology
Volume: 245
Issue: 1-2
Pages: 75-78
DOI
Related Report
Peer Reviewed
-
[Journal Article] Antibodies against muscle-specific kinase impair both presynaptic and postsynaptic functions in a murine model of myasthenia gravis2012
Author(s)
Mori S, Kubo S, Akiyoshi T, Yamada S, Miyazaki T, Hotta H, Desaki J, Kishi M, Konishi T, Nishino Y, Miyazawa A, Maruyama N, Shigemoto K
-
Journal Title
The American Journal of Pathology
Volume: 180
Issue: 2
Pages: 617-28
DOI
Related Report
Peer Reviewed
-
[Journal Article] Owing to Low-Turnover Osteoporosis and Impaired CollagenCross-Linking2011
Author(s)
Hidetoshi Nojiri, Yoshitomo Saita, Daichi Morikawa, Keiji Kobayashi, Chizuru Tsuda, Tsuyoshi Miyazaki, Mitsuru Saito, Keishi Marumo, Ikuho Yonezawa, Kazuo Kaneko, Takuji Shirasawa, and Takahiko Shimizu
-
Journal Title
J Bone Miner Res
Volume: 26(11)
Issue: 11
Pages: 2682-94
DOI
Related Report
Peer Reviewed
-
[Journal Article] Neutrophil CD64 expression as a diagnostic marker for local infection and crystal-induced arthritis2010
Author(s)
Toru Doi, Tsuyoshi Miyazaki, Jinju Nishino, Sakae Tanaka, Toshihiro Matsui, Akiko Komiya, Seizo Yamamoto, Fumiaki Tokimura, Toshihito Mori, Keita Nishimura, Narutaka Katoh, Jun Hasegawa, Yasunori Omata, Takashi Matsushita, Shigeto Tohma
-
Journal Title
Mod Rheumatol
Volume: 20(6)
Issue: 6
Pages: 573-9
DOI
NAID
Related Report
Peer Reviewed
-
-
[Journal Article] Muscle weakness and neuromuscular junctions in aging and disease2010
Author(s)
Shigemoto, K., Kubo, S., Mori, S., Yamada, S., Akiyoshi, T., and Miyazaki, T.
-
Journal Title
Geriatr Gerontol Int 10 Suppl
Volume: 1
Issue: s1
Pages: 137-147
DOI
NAID
Related Report
Peer Reviewed
-
-
-
[Journal Article] The antiapoptotic protein Bcl-xL negatively regulates the bone-resorbing activity of osteoclasts in mice2009
Author(s)
Iwasawa M, Miyazaki T, Nagase Y, Akiyama T, Kadono Y, Nakamura M, Oshima Y, Yasui T, Matsumoto T, Nakamura T, Kato S, Hennighausen L, Nakamura K, Tanaka S
-
Journal Title
J Clin Invest
Volume: 119(10)
Pages: 3149-59
DOI
Related Report
Peer Reviewed
-
-
-
[Journal Article] The antiapoptotic protein Bcl-xL negatively regulates the bone-resorbing activity of osteoclasts in mice2009
Author(s)
Iwasawa M, Miyazaki T, Nagase Y, Akiyama T, Kadono Y, Nakamura M, Oshima Y, Yasui T, Matsumoto T, Nakamura T, Kato S, Hennighausen L, Nakamura K, Tanaka S
-
Journal Title
J Clin Invest. 119
Pages: 3149-59
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-