Identification and functional analysis of a novel substrate of Pdk4 in the regulation of osteoclastogenesis in the unloaded condition

• Project/Area Number: 24659829
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Functional basic dentistry
• Research Institution: Nagasaki University
• Principal Investigator: KOMORI Toshihisa 長崎大学, 医歯(薬)学総合研究科, 教授 (00252677)
• Co-Investigator(Kenkyū-buntansha): MORIISHI Takeshi 長崎大学, 大学院医歯薬学総合研究科, 助教 (20380983)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 骨細胞 / 破骨細胞 / 廃用性骨粗鬆症 / メカニカルストレス / Pdk4

Research Abstract

Bone mass is increase by exercise and reduced by long-term bed rest, immobilization caused by nerve injury, and microgravity in the space. These non-weight bearing conditions cause disuse osteoporosis. Osteocyte network, which is embedded in bone, is responsible for the sensing of mechanical stress and the transduction of the signal to osteoblasts and osteoclasts in the bone surface, and regulates bone mass. Pdk4, which is a kinase that inhibits energy production in mitochondria, was upregulated in osteoblasts and osteocytes in the unloaded condition of adult mice. Bone loss in the unloaded condition was not caused in Pdk4 adult knockout mice, indicating that Pdk4 is involved in bone loss in the unloaded condition of adult mice.

Research Products

• [Journal Article] Bcl2 deficiency activates FoxO through Akt inactivation and accelerates osteoblast differentiation (2014)
  • Author(s): Moriishi T, Kawai Y, Komori H, Rokutanda S, Eguchi Y, Tsujimoto Y, Asahina I, Komori T
  • Journal Title: PLoS One Volume: 9(1) Issue: 1 Pages: 86629-86629
  • DOI: 10.1371/journal.pone.0086629
  • NAID: 120006987119
  • Peer Reviewed / Open Access
• [Journal Article] Filamin-interacting proteins, Cfm1 and Cfm2, are essential for the formation of cartilaginous skeletal elements (2014)
  • Author(s): Mizuhashi K, Komori T, Furukawa, T(他7名)
  • Journal Title: Hum Mol Genet Volume: Vol.23 Pages: 2953-67
  • Peer Reviewed
• [Journal Article] Dlx5 and Mef2 Regulate a Novel Runx2 Enhancer for Osteoblast-Specific Expression. (2014)
  • Author(s): Kawane T, Komori H, Liu W, Moriishi T, Miyazaki T, Mori M, Matsuo Y, Takada Y, Izumi S, Jiang Q, Nishimura R, Kawai Y, Komori T.
  • Journal Title: Journal of bone and mineral research Volume: - Issue: 9 Pages: 1960-1969
  • DOI: 10.1002/jbmr.2240
  • Peer Reviewed
• [Journal Article] Filamin-interacting proteins, Cfm1 and Cfm2, are essential for the formation of cartilaginous skeletal elements. (2014)
  • Author(s): Mizuhashi K, Kanamoto T, Moriishi T, Muranishi Y, Miyazaki T, Terada K, Omori Y, Ito M, Komori T, Furukawa T.
  • Journal Title: Human molecular genetics Volume: - Issue: 11 Pages: 2953-2967
  • DOI: 10.1093/hmg/ddu007
  • Peer Reviewed / Open Access
• [Journal Article] Pin1-mediated Runx2 modification is critical for skeletal development (2013)
  • Author(s): Yoon WJ, Islam R, Cho YD, Woo KM, Baek JH, Uchida T, Komori T, van Wijnen A,Stein JL, Lian JB, Stein GS, Choi JY, Bae SC, Ryoo HM
  • Journal Title: J Cell Physiol Volume: Vol.228 Pages: 2377-85
  • Peer Reviewed
• [Journal Article] Novel sandwich ELISAs for rat DMP1 : age-related decrease of circulatory DMP1 levels in male rats (2013)
  • Author(s): Sato S, Hashimoto J, Usami Y, Ohyama K, Isogai Y, Hagiwara Y, Maruyama N, Komori T, Kuroda T, Toyosawa S
  • Journal Title: Bone Volume: Vol.57 Pages: 429-436
  • Peer Reviewed
• [Journal Article] Overexpression of Cdk6 and Ccnd1 in chondrocytes inhibited chondrocyte maturation and caused p53dependent apoptosis without enhancing proliferation (2013)
  • Author(s): Ito K, Maruyama Z, Sakai A, Izumi S, Moriishi T, Yoshida CA, Miyazaki T, Komori H, Takada K, Kawaguchi H, Komori T
  • Journal Title: Oncogene Volume: Vol.33 Pages: 1862-71
  • Peer Reviewed
• [Journal Article] Functions of the osteocyte network in the regulation of bone mass (2013)
  • Author(s): Komori T
  • Journal Title: Cell Tissue Res Volume: Vol.352 Pages: 191-198
  • NAID: 120006986155
  • Peer Reviewed
• [Journal Article] MAML1 enhances the transcriptional activity of Runx2 and plays a role in bone development (2013)
  • Author(s): Watanabe T, Komori T, Asahara H (他10名)
  • Journal Title: PLos Genet Volume: 9(1) Issue: 1 Pages: 1003132-1003132
  • DOI: 10.1371/journal.pgen.1003132
  • NAID: 120006985752
  • Peer Reviewed
• [Journal Article] Thrombospondin-1 is a putative target gene of runx2 and runx3. (2013)
  • Author(s): Shi X, Deepak V, Wang L, Ba X, Komori T, Zeng X, Liu W.
  • Journal Title: International journal of molecular sciences [electronic resource] Volume: 14 Issue: 7 Pages: 14321-14332
  • DOI: 10.3390/ijms140714321
  • NAID: 120006986154
  • Peer Reviewed
• [Journal Article] Pin1-mediated Runx2 modification is critical for skeletal development. (2013)
  • Author(s): Yoon WJ, Islam R, Cho YD, Woo KM, Baek JH, Uchida T, Komori T, van Wijnen A,Stein JL, Lian JB, Stein GS, Choi JY, Bae SC, Ryoo HM.
  • Journal Title: Journal of cellular physiology Volume: 228 Issue: 12 Pages: 2377-2385
  • DOI: 10.1002/jcp.24403
  • Peer Reviewed
• [Journal Article] Novel sandwich ELISAs for rat DMP1: age-related decrease of circulatory DMP1 levels in male rats. (2013)
  • Author(s): Sato S, Hashimoto J, Usami Y, Ohyama K, Isogai Y, Hagiwara Y, Maruyama N, Komori T, Kuroda T, Toyosawa S.
  • Journal Title: Bone Volume: 57 Issue: 2 Pages: 429-436
  • DOI: 10.1016/j.bone.2013.09.013
  • Peer Reviewed
• [Journal Article] Regulation of Rb family proteins by Cdk6/Ccnd1 in growth plates. (2013)
  • Author(s): Komori T
  • Journal Title: Cell Cycle Volume: 12 Issue: 14 Pages: 2161-2162
  • DOI: 10.4161/cc.25515
  • NAID: 120006986153
• [Journal Article] Overexpression of Cdk6 and Ccnd1 in chondrocytes inhibited chondrocyte maturation and caused p53dependent apoptosis without enhancing proliferation. (2013)
  • Author(s): Ito K, Maruyama Z, Sakai A, Izumi S, Moriishi T, Yoshida CA, Miyazaki T, Komori H, Takada K, Kawaguchi H, Komori T.
  • Journal Title: Oncogene Volume: 33 Issue: 14 Pages: 1862-1871
  • DOI: 10.1038/onc.2013.130
  • Peer Reviewed
• [Journal Article] Functions of the osteocyte network in the regulation of bone mass. (2013)
  • Author(s): Komori T
  • Journal Title: Cell and tissue research Volume: 352 Issue: 2 Pages: 191-198
  • DOI: 10.1007/s00441-012-1546-x
  • NAID: 120006986155
  • Peer Reviewed
• [Journal Article] Galnt3 deficiency disrupts acrosome formation and leads to oligoasthenoteratozoos permia (2013)
  • Author(s): 宮崎 敏博
  • Journal Title: Histochemistry and Cell Biology Volume: 139 Issue: 2 Pages: 339-354
  • DOI: 10.1007/s00418-012-1031-3
  • Peer Reviewed
• [Journal Article] Osteocyte network; a negative regulatory system for bone mass augmented by the induction of Rankl in osteoblasts and Sost in osteocytes at unloading (2012)
  • Author(s): Moriishi T, Fukuyama R, Ito M, Miyazaki T, Maeno T, Kawai Y, Komori H, Komori T
  • Journal Title: PLoS One Volume: 7(6) Issue: 6 Pages: 40143-40143
  • DOI: 10.1371/journal.pone.0040143
  • NAID: 120006985704
  • Peer Reviewed
• [Journal Article] Calcium/calmodulin-signaling supports TRPV4 activation in osteoclasts and regulates bone mass (2012)
  • Author(s): Masuyama R, Mizuno A, Komori H, Kajiya H, Uekawa A, Kitaura H, Okabe K, Ohyama K, Komori T
  • Journal Title: J Bone Miner Res Volume: Vol.27 Pages: 1708-1721
  • Peer Reviewed
• [Journal Article] In situ differentiation of CD8ααT cells from CD4T cells in peripheral lymphoid tissues. (2012)
  • Author(s): Nambu Y
  • Journal Title: Scientific reports Volume: 2 Pages: 642-642
  • Peer Reviewed
• [Journal Article] Chronological histological changes during bone regeneration on a non-crosslinked atelocollagen matrix. (2012)
  • Author(s): Kagawa R
  • Journal Title: Journal of bone and mineral metabolism Volume: 30 Issue: 6 Pages: 638-650
  • DOI: 10.1007/s00774-012-0376-y
  • Peer Reviewed
• [Journal Article] Interaction of Tmem119 and the bone morphogenetic protein pathway in the commitment of myoblastic into osteoblastic cells. (2012)
  • Author(s): Tanaka K
  • Journal Title: Bone Volume: 51 Issue: 1 Pages: 158-167
  • DOI: 10.1016/j.bone.2012.04.017
  • Peer Reviewed
• [Journal Article] Calcium/calmodulin-signaling supports TRPV4 activation in osteoclasts and regulates bone mass. (2012)
  • Author(s): Masuyama R
  • Journal Title: Journal of bone and mineral research Volume: 27 Issue: 8 Pages: 1708-1721
  • DOI: 10.1002/jbmr.1629
  • Peer Reviewed
• [Presentation] 骨細胞ネットワークによるメカニカルストレス応答 (2013)
  • Author(s): 小守壽文
  • Organizer: 第55回歯科基礎医学会学術大会・総会
  • Place of Presentation: 岡山コンベンションセンター(岡山県)
• [Presentation] Roles of Cbfb in bone development during embryonic stage and after birth (2013)
  • Author(s): 小守壽文
  • Organizer: The EMBO Workshop RUNX transcription factors in development and disease
  • Place of Presentation: Wilsede,Germany
• [Presentation] Osteocytes, Coordinator of the Bone (2013)
  • Author(s): 小守壽文
  • Organizer: 2013 Seoul International Congress of Endocrinology and Metabolism
  • Place of Presentation: Grand Hilton Seoul Hotel, Korea
• [Presentation] Osteocyte network and mechanical stress (2013)
  • Author(s): 小守壽文
  • Organizer: 第22回国際リウマチシンポジウム
  • Place of Presentation: 国立京都国際会館(京都府)
• [Presentation] Osteocyte network and mechanical stress. (2013)
  • Author(s): Toshihisa Komori
  • Organizer: The 22nd International Rheumatology Symposium
  • Place of Presentation: 京都市 国立京都国際会館
• [Presentation] Osteocytes, Coordinator of the Bone. (2013)
  • Author(s): Toshihisa Komori
  • Organizer: 2013 Seoul International Congress of Endocrinology and Metabolism
  • Place of Presentation: Grand Hilton Seoul Hotel, Korea
  • Invited
• [Presentation] Proliferation, differentiation, and apoptosis in chondrocyte. (2013)
  • Author(s): Toshihisa Komori
  • Organizer: 2013 Seoul International Congress of Endocrinology and Metabolism
  • Place of Presentation: Grand Hilton Seoul Hotel, Korea
  • Invited
• [Presentation] Roles of Cbfb in bone development during embryonic stage and after birth. (2013)
  • Author(s): Toshihisa Komori
  • Organizer: The EMBO Workshop RUNX transcription factors in development and disease, Germany
  • Place of Presentation: Wilsede,Germany
• [Presentation] 骨細胞ネットワークによるメカニカルストレス応答 (2013)
  • Author(s): 小守壽文
  • Organizer: 第55回歯科基礎医学会学術大会・総会
  • Place of Presentation: 岡山市 岡山コンベンションセンター
• [Presentation] 骨芽細胞分化および血管新生におけるSp7の役割 (2013)
  • Author(s): 小守寿人、小守壽文
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸市 神戸ポートアイランド
• [Remarks]
  • URL: http://www.de.nagasaki-u.ac.jp/dokuji/kaibou-2/index.html
• [Remarks] 長崎大学細胞生物学分野ホームページ
  • URL: http://www.de.nagasaki-u.ac.jp/dokuji/kaibou-2/
• [Patent(Industrial Property Rights)] 荷重感知遺伝子 (2011)
  • Inventor(s): 小守壽文
  • Industrial Property Rights Holder: 長崎大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2011-138935
  • Filing Date: 2011-06-22