Regulation of osteoclastogenesis by transcriptional repressor Blimp1 via epigenetic regulation

• Project/Area Number: 23592231
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Keio University
• Principal Investigator: MIYAUCHI Yoshiteru 慶應義塾大学, 医学部, 共同研究員 (90445411)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 破骨細胞 / 骨粗鬆症 / 骨代謝 / 転写因子

Research Abstract

Osteoclasts are unique bone resorbing cells, and thus are therapeutic targets to treat bone diseases such as osteoporosis. We found that B lymphocyte induced maturation protein 1 (Blimp1), a transcriptional repressor, was required for osteoclastogenesis. Although Blimp1-null mutant mice are embryonic lethal, Blimp1 conditional knockout at an adult stage by a Cre/loxP system did not promote lethal adverse effects in mice, while resulted in significant inhibition of osteoclast formation with increased bone mass. Thus, Blimp1 was considered as a therapeutic target to treat skeletal diseases such as osteoporosis (J Biol Chem 2012).

Research Products

• [Journal Article] HIF1α is required for osteoclast activation by estrogen deficiency in postmenopausal osteoporosis. (2013)
  • Author(s): Miyauchi Y, Sato Y, Kobayashi T, Yoshida S, Mori T, Kanagawa H, Katsuyama E, Fujie A, Hao W, Miyamoto K, Tando T, Morioka H, Matsumoto M, Chambon P, Johnson RS, Kato S, Toyama Y, Miyamoto T.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 110 Issue: 41 Pages: 16568-16573
  • DOI: 10.1073/pnas.1308755110
  • Peer Reviewed
• [Journal Article] An essential role for STAT6-STAT1 protein signaling in promoting macrophage cell-cell fusion (2012)
  • Author(s): Miyamoto H, Katsuyama E, Miyauchi Y, Hoshi H, Miyamoto K, Sato Y, Kobayashi T, Iwasaki R, Yoshida S, Mori T, Kanagawa H, Fujie A, Hao W, Morioka H, Matsumoto M, Toyama Y, Miyamoto T
  • Journal Title: J Biol Chem Volume: vol. 287 Issue: 39 Pages: 32479-84
  • DOI: 10.1074/jbc.m112.358226
  • Peer Reviewed
• [Journal Article] Conditional inactivation of Blimp1 in adult mice promotes increased bone mass. (2012)
  • Author(s): Miyauchi Y, Miyamoto H, Yoshida S, Mori T, Kanagawa H, Katsuyama E, Fujie A, Hao W et al.
  • Journal Title: J Biol Chem Volume: 287 Issue: 34 Pages: 28508-28517
  • DOI: 10.1074/jbc.m112.356634
  • Peer Reviewed
• [Journal Article] PDGFBB promotes PDGFRα-positive cell migration into artificial bone in vivo. (2012)
  • Author(s): Yoshida S, Iwasaki R, Kawana H, Miyauchi Y, Hoshi H, Miyamoto H, Mori T, Kanagawa H et al.
  • Journal Title: Biochem Biophys Res Commun. Volume: 421 Issue: 4 Pages: 785-789
  • DOI: 10.1016/j.bbrc.2012.04.084
  • Peer Reviewed
• [Journal Article] Aldehyde-stress resulting from Aldh2 mutation promotes osteoporosis due to impaired osteoblastogenesis (2012)
  • Author(s): Hoshi H, Hao W, Fujita Y, Funayama A, Miyauchi Y, Hashimoto K, Miyamoto K, (他21名)
  • Journal Title: J. Bone Miner Res Volume: 27(9) Issue: 9 Pages: 2015-2023
  • DOI: 10.1002/jbmr.1634
  • Peer Reviewed
• [Journal Article] OC-STAMP and DC-STAMP cooperatively modulate cell-cell fusion to form osteoclasts and foreign body giant cells (2012)
  • Author(s): Miyamoto H, et al
  • Journal Title: J Bone Miner Res Volume: (In press) Issue: 6 Pages: 1289-1297
  • DOI: 10.1002/jbmr.1575
  • Peer Reviewed
• [Journal Article] In vivo behavior of multiple myeloma cells and their niche in immunodeficient mice (2012)
  • Author(s): Iriuchishima H, Kizaki M, et al
  • Journal Title: PLoS ONE Volume: 7(2) Issue: 2 Pages: e30557-e30557
  • DOI: 10.1371/journal.pone.0030557
  • Peer Reviewed
• [Journal Article] An essential role for STAT6-STAT1 protein signaling in promoting macrophage cell-cell fusion. (2012)
  • Author(s): Miyamoto H, Katsuyama E, Miyauchi Y, Hoshi H, Miyamoto K, Sato Y, Kobayashi T, Iwasaki R et al.
  • Journal Title: J Biol Chem Volume: 287 Pages: 32478-32484
  • Peer Reviewed
• [Journal Article] Neovascular niche for human myeloma cells in immunodeficient mouse bone. (2012)
  • Author(s): Iriuchishima H, Takubo K, Miyakawa Y, Nakamura-Ishizu A, Miyauchi Y, Fujita N, Miyamoto K, Miyamoto T, Ikeda E, Kizaki M, Nojima Y, Suda T.
  • Journal Title: PLoS One. Volume: 7
  • Peer Reviewed
• [Journal Article] Osteoclasts are dispensable for haematopoietic stem cell maintenance and mobilization (2011)
  • Author(s): Miyamoto K, et al
  • Journal Title: J Exp Med Volume: 208 Issue: 11 Pages: 2175-2181
  • DOI: 10.1084/jem.20101890
  • Peer Reviewed
• [Journal Article] The IRE1α-XBP1 pathway is essential for osteoblast differentiation through promoting transcription of Osterix. (2011)
  • Author(s): Tohmonda T, Miyauchi Y, Ghosh R, Yoda M, Uchikawa S, Takito J, Morioka H, Nakamura M, Iwawaki T, Chiba K, Toyama Y, Urano F, Horiuchi K.
  • Journal Title: EMBO Rep. Volume: 12 Pages: 451-457
  • Peer Reviewed
• [Journal Article] Suppressive effects for osteoclastogenesis regulated by RANKL signal. (2011)
  • Author(s): Miyauchi Y, Miyamoto T.
  • Journal Title: Clin Calcium. Volume: 21 Pages: 1141-1147
• [Journal Article] Matrix metalloproteinase 13 in the ligamentum flavum from lumbar spinal canal stenosis patients with and without diabetes mellitus. (2011)
  • Author(s): Cui G, Watanabe K, Miyauchi Y, Hosogane N, Tsuji T, Ishii K, Nakamura M, Toyama Y, Chiba K, Miyamoto T, Matsumoto M.
  • Journal Title: J Orthop Sci. Volume: 16 Pages: 785-790
  • Peer Reviewed
• [Journal Article] Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization. (2011)
  • Author(s): Miyamoto K, Yoshida S, Kawasumi M, Hashimoto K, Kimura T, Sato Y, Kobayashi T, Miyauchi Y, Morioka H, Chiba K, Kobayashi T, Yasuda H, Penninger JM, Toyama Y, Suda T, Miyamoto T.
  • Journal Title: J Exp Med. Volume: 208 Pages: 2175-2181
  • Peer Reviewed
• [Presentation] 転写抑制因子Blimp1は骨代謝制御の分子標的である (2011)
  • Author(s): 宮内芳輝、戸山芳昭、宮本健史
  • Organizer: 第29回日本骨代謝学会学術集会
  • Place of Presentation: 大阪国際会議場
• [Presentation] 転写抑制因子Blimp1は骨量制御の分子標的である (2011)
  • Author(s): 宮内芳輝、戸山芳昭、宮本健史
  • Organizer: 第２９回日本骨代謝学会
  • Place of Presentation: 大阪国際会議場（大阪府）