Analysis of bone selective androgen and estrogen receptor modulators.

• Project/Area Number: 24790071
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Tokyo University of Agriculture and Technology
• Principal Investigator: HIRATA MICHIKO 東京農工大学, 工学(系)研究科(研究院), 講師 (40544060)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 骨粗鬆症 / エストロゲン / アンドロゲン / 受容体作働薬

Research Abstract

Bone remodeling is regulated by bone resorption and formation. Estrogen deficiency induced by menopause results in marked bone loss in women. The elderly men exhibit marked bone loss due to androgen deficiency. We developed the new osteoporosis drugs with minimal undesired effects on reproductive tissues. Carboranes restored bone loss in orchidectomized mice without androgenic action in the sex organs. These result indicated that Carboranes are novel selective androgen receptor modulators (SARM) that may offer a new therapy option for osteoporosis.

Research Products

• [Journal Article] The protective effects ofβ-cryptoxanthin on inflammatory bone resorption in a mouse experimental model of periodontitis (2013)
  • Author(s): Matsumoto C, Ashida N, Yokoyama S, Tominari T, Hirata M, Ogawa K, Sugiura M, Yano M, Inada M, Miyaura C
  • Journal Title: Biosci. Biotechnol. Biochem Volume: 77(4) Pages: 860-862
  • Peer Reviewed
• [Journal Article] The protective effects of β-cryptoxanthin on inflammatory bone resorption in a mouse experimental model of periodontitis. (2013)
  • Author(s): Matsumoto C
  • Journal Title: Biosci. Biotechnol. Biochem. Volume: 77(4) Pages: 860-862
  • Peer Reviewed
• [Journal Article] Toll-like receptor 2 heterodimers, TLR2/6 and TLR2/1, induce prostaglandin E production by osteoblasts, osteoclast formation and inflammatory periodontitis (2012)
  • Author(s): Matsumoto C, Oda T, Yokoyama S, Tominari T, Hirata M, Miyaura C, Inada M
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 428(1) Pages: 110-115
  • Peer Reviewed
• [Journal Article] Synthesis of vitamin D(3) derivatives with nitrogen-linked substituents at A-ring C-2 and evaluation of their vitamin D receptor-mediated transcriptional activity (2012)
  • Author(s): Abe J, Nagai Y, Higashikuni R, Iida K, Hirokawa T, Nagai H, Kominato K, Tsuchida T, Hirata M, Inada M, Miyaura C, Nagasawa K
  • Journal Title: Org Biomol Chem Volume: 10(38) Pages: 7826-7839
  • Peer Reviewed
• [Journal Article] Toll-like receptor 2 heterodimers, TLR2/6 and TLR2/1, induce prostaglandin E production by osteoblasts, osteoclast formation and inflammatory periodontitis. (2012)
  • Author(s): Matsumoto C
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 428（1） Issue: 1 Pages: 110-115
  • DOI: 10.1016/j.bbrc.2012.10.016
  • Peer Reviewed
• [Journal Article] Synthesis of vitamin D(3) derivatives with nitrogen-linked substituents at A-ring C-2 and evaluation of their vitamin D receptor-mediated transcriptional activity. (2012)
  • Author(s): Abe J
  • Journal Title: Org Biomol Chem. Volume: 10(38) Issue: 38 Pages: 7826-7839
  • DOI: 10.1039/c2ob26017d
  • Peer Reviewed
• [Journal Article] Polymethoxy flavonoids, nobiletin and tangeretin, prevent lipopolysaccharide-induced inflammatory bone loss in an experimental model for periodontitis. (2012)
  • Author(s): Tominari T
  • Journal Title: J. Pharmacol. Sci. Volume: 119(4) Pages: 390-394
  • Peer Reviewed
• [Journal Article] Capsaicin, a TRPV1 ligand, suppresses boneresorption n by inhibiting theprostaglandin E production of osteoblasts, and attenuates the inflammatory bone loss induced by lipopolysaccharide (2012)
  • Author(s): Kobayashi M, Watanabe K, Yokoyama S, Matsumoto C, Hirata M, Tominari T, Inada M and Miyaura C
  • Journal Title: ISRN. Phamacol Volume: 2012 Pages: 439860-439860
  • DOI: 10.5402/2012/439860
  • Peer Reviewed
• [Presentation] PGE2 receptor EP4 regulates breast cancer metastasis and bone resorption through osteoblastic RANKL production (2013)
  • Author(s): Yokoyama S, Watanabe K, Hirata M, Matsumoto C, Maruyama T, Miyaura C, Inada M
  • Organizer: ASBMR 2013 Annual Meeting
  • Place of Presentation: Baltimore Convention Center in Baltimore, Maryland, USA.
  • Year and Date: 2013-10-07
• [Presentation] Bone metastatic melanoma promotes angiogenesis with the production of prostaglandin E2 by host stromal cells (2013)
  • Author(s): Watanabe K, Yokoyama S, Matsumoto C, Hirata M, Inada M , Miyaura C
  • Organizer: ASBMR 2013 Annual Meeting
  • Place of Presentation: Baltimore Convention Center in Baltimore, Maryland, USA(Poster Sessions(ポスター))
  • Year and Date: 2013-10-06
• [Presentation] PGE2 receptor EP4 regulates breast cancer metastasis and bone resorption through osteoblastic RANKL production (2013)
  • Author(s): Yokoyama S, Watanabe K, Hirata M, Matsumoto C, Maruyama T, Miyaura C, Inada M
  • Organizer: FR0459 Plenary Sessions. ASBMR 2013 Annual Meeting
  • Place of Presentation: Baltimore Convention Center in Baltimore, Maryland, USA(口頭発表)
  • Year and Date: 2013-10-05
• [Presentation] EP4受容体は骨芽細胞のRANKL発現を介して乳癌の骨吸収を制御する (2013)
  • Author(s): 横山智史,松本千穂,平田美智子,丸山隆幸,稲田全規,宮浦千里
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜(神奈川県)(ポスター発表)
  • Year and Date: 2013-09-13
• [Presentation] 前立腺癌細胞のグルコース代謝と増殖調節への関与 (2013)
  • Author(s): 木内絵梨奈,渡邊健太,平田美智子,稲田全規,宮浦千里
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜(神奈川県)(ポスター発表)
  • Year and Date: 2013-09-13
• [Presentation] Effects of a carbon-containing polyhedral boron-cluster compound BA321 on bone loss due to sex steroid deficiency by AR- and ER-dependent mechanism (2013)
  • Author(s): Matsumoto C, Hirata M, Inada M , Miyaura C
  • Organizer: ASBMR 2013 Annual Meeting
  • Place of Presentation: Baltimore Convention Center in Baltimore, Maryland, USA(Poster Sessions(ポスター))
  • Year and Date: 2013-09-12
• [Presentation] Bone malignant melanoma induces angiogenesis with the production of prostaglandin E2 by host stromal cells (2013)
  • Author(s): 渡邊健太、横山智史、松本千穂、平田美智子、宮浦千里、稲田全規
  • Organizer: 国際骨代謝学会(IBMS)・日本骨代謝学会(JSBMR)第2回合同国際会議口頭発表(Young Investigator)
  • Place of Presentation: 神戸コンベンションセンター・神戸ポートピアホテル(兵庫県)(ポスター発表)
  • Year and Date: 2013-06-01
• [Presentation] mTORの活性阻害による前立腺癌細胞の増殖抑制 (2013)
  • Author(s): 根本康利,渡邊健太,平田美智子,稲田全規,宮浦千里
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜(神奈川県)(ポスター発表)
  • Year and Date: 2013-05-31
• [Presentation] PGE2 regulates breast cancer metastasis and osteoblastic RANKL expression through its receptor subtype EP4 (2013)
  • Author(s): 横山智史、渡邊健太、平田美智子、松本千穂、稲田全規、宮浦千里
  • Organizer: 国際骨代謝学会(IBMS)・日本骨代謝学会(JSBMR)第2回合同国際会議
  • Place of Presentation: 神戸コンベンションセンター・神戸ポートピアホテル(兵庫県)(口頭発表)
  • Year and Date: 2013-05-31
• [Presentation] 前立腺癌の浸潤と骨破壊におけるマトリックスプロテアーゼ(MMPs)の関与 (2012)
  • Author(s): 渡邊健太,横山智史,松本千穂,平田美智子,宮浦千里,稲田全規
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡(福岡県)(ポスター発表)
  • Year and Date: 2012-12-16
• [Presentation] Effects of a carbon-containing polyhedral boron-cluster compound BA321 on bone loss due to sex steroid deficiency by AR- and ER- dependent mechanism (2012)
  • Author(s): 松本千穂、稲田全規、平田美智子、宮浦千里
  • Organizer: 国際骨代謝学会(IBMS)・日本骨代謝学会(JSBMR)第2回合同国際会議
  • Place of Presentation: 神戸コンベンションセンター・神戸ポートピアホテル(兵庫県)(ポスター発表)
  • Year and Date: 2012-12-15
• [Presentation] In Vivoイメージングによる乳癌増殖の経時的な全身解析法 (2012)
  • Author(s): 増田光章,横山智史,渡邊健太,平田美智子,宮浦千里,稲田全規
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡(福岡県)(ポスター発表)
  • Year and Date: 2012-12-15
• [Presentation] 乳癌骨転移における宿主反応とPGE2/EP4シグナルの関与 (2012)
  • Author(s): 横山智史,松本千穂,平田美智子,丸山隆幸,宮浦千里,稲田全規
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡(福岡県)(ポスター発表)
  • Year and Date: 2012-12-15
• [Presentation] 1型コラーゲンによる癌細胞増殖制御の解析 (2012)
  • Author(s): 金田真雪,渡邊健太,平田美智子,宮浦千里,稲田全規
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡(福岡県)(ポスター発表)
  • Year and Date: 2012-12-15
• [Presentation] 細胞外マトリックス分解と前立腺癌の浸潤 (2012)
  • Author(s): 加藤綾華,渡邊健太,平田美智子,宮浦千里,稲田全規
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡(福岡県)(ポスター発表)
  • Year and Date: 2012-12-15
• [Presentation] Toll-like receptor 2へテロ受容体(TLR1/2, TLR 2/6)シグナルによる骨吸収亢進のメカニズム (2012)
  • Author(s): 松本千穂,小田俊男,冨成司,平田美智子,稲田全規,宮浦千里
  • Organizer: 第30回日本骨代謝学会
  • Place of Presentation: 京王プラザホテル(東京都)(口演7「シグナル伝達・転写因子」)
  • Year and Date: 2012-07-20
• [Presentation] 悪性黒色腫におけるメラニン産生機構の解析 (2012)
  • Author(s): 冨田夏美,横山智史,平田美智子,稲田全規,宮浦千里
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡(福岡県)(ポスター発表)
• [Presentation] （口頭発表） PGE2 receptor EP4 regulates breast cancer metastasis and bone resorption through osteoblastic RANKL production.
  • Author(s): Yokoyama S, Watanabe K, Hirata M, Matsumoto C, Maruyama T, Miyaura C, Inada M
  • Organizer: ASBMR 2013 Annual Meeting
  • Place of Presentation: Baltimore Convention Center in Baltimore, Maryland, USA.
• [Presentation] （ポスター） PGE2 receptor EP4 regulates breast cancer metastasis and bone resorption through osteoblastic RANKL production.
  • Author(s): Yokoyama S, Watanabe K, Hirata M, Matsumoto C, Maruyama T, Miyaura C, Inada M
  • Organizer: ASBMR 2013 Annual Meeting
  • Place of Presentation: Baltimore Convention Center in Baltimore, Maryland, USA.
• [Presentation] Bone metastatic melanoma promotes angiogenesis with the production of prostaglandin E2 by host stromal cells.
  • Author(s): Watanabe K, Yokoyama S, Matsumoto C, Hirata M, Inada M , Miyaura C
  • Organizer: ASBMR 2013 Annual Meeting
  • Place of Presentation: Baltimore Convention Center in Baltimore, Maryland, USA.
• [Presentation] Effects of a carbon-containing polyhedral boron-cluster compound BA321 on bone loss due to sex steroid deficiency by AR- and ER-dependent mechanism.
  • Author(s): Matsumoto C, Hirata M, Inada M , Miyaura C
  • Organizer: ASBMR 2013 Annual Meeting
  • Place of Presentation: Baltimore Convention Center in Baltimore, Maryland, USA.
• [Presentation] EP4受容体は骨芽細胞のRANKL発現を介して乳癌の骨吸収を制御する
  • Author(s): 横山智史, 松本千穂,平田美智子,丸山隆幸, 稲田全規,宮浦千里
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] 前立腺癌細胞のグルコース代謝と増殖調節への関与
  • Author(s): 木内絵梨奈,渡邊健太,平田美智子,稲田全規,宮浦千里
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] mTORの活性阻害による前立腺癌細胞の増殖抑制
  • Author(s): 根本康利,渡邊健太,平田美智子,稲田全規,宮浦千里
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] PGE2 regulates breast cancer metastasis and osteoblastic RANKL expression through its receptor subtype EP4.
  • Author(s): 横山智史、渡邊健太、平田美智子、松本千穂、稲田全規、宮浦千里
  • Organizer: 国際骨代謝学会（IBMS）・日本骨代謝学会（JSBMR）第2回合同国際会議
  • Place of Presentation: 神戸コンベンションセンター・神戸ポートピアホテル（兵庫県）
• [Presentation] Bone malignant melanoma induces angiogenesis with the production of prostaglandin E2 by host stromal cells.
  • Author(s): 渡邊健太、横山智史、松本千穂、平田美智子、宮浦千里、稲田全規
  • Organizer: 国際骨代謝学会（IBMS）・日本骨代謝学会（JSBMR）第2回合同国際会議
  • Place of Presentation: 神戸コンベンションセンター・神戸ポートピアホテル（兵庫県）
• [Presentation] Effects of a carbon-containing polyhedral boron-cluster compound BA321 on bone loss due to sex steroid deficiency by AR- and ER- dependent mechanism.
  • Author(s): 松本千穂、稲田全規、平田美智子、宮浦千里
  • Organizer: 国際骨代謝学会（IBMS）・日本骨代謝学会（JSBMR）第2回合同国際会議
  • Place of Presentation: 神戸コンベンションセンター・神戸ポートピアホテル（兵庫県）
• [Presentation] 悪性黒色腫におけるメラニン産生機構の解析
  • Author(s): 冨田夏美
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡国際会議場
• [Presentation] In Vivoイメージングによる乳癌増殖の経時的な全身解析法
  • Author(s): 増田光章
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡国際会議場
• [Presentation] 乳癌骨転移における宿主反応とPGE2/EP4シグナルの関与
  • Author(s): 横山智史
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡国際会議場
• [Presentation] 1型コラーゲンによる癌細胞増殖制御の解析
  • Author(s): 金田真雪
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡国際会議場
• [Presentation] 細胞外マトリックス分解と前立腺癌の浸潤
  • Author(s): 加藤綾華
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡国際会議場
• [Presentation] 前立腺癌の浸潤と骨破壊におけるマトリックスプロテアーゼ（MMPs）の関与
  • Author(s): 渡邊健太
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡国際会議場
• [Presentation] Carborane BA321, One of The Carbon-containing Polyhedral Boroncluster Compounds, is A New Type of Selective Androgen Receptor Modulator.
  • Author(s): Matsumoto C
  • Organizer: American Society For Bone and Mineral Research 2012
  • Place of Presentation: Minneapolis, Minnesota, USA
• [Presentation] Angiogenesis with Bone Malignant Melanoma Induces Production of Prostaglandin E2 in Host Stromal Cells.
  • Author(s): Watanabe K
  • Organizer: American Society For Bone and Mineral Research 2012
  • Place of Presentation: Minneapolis, Minnesota, USA
• [Presentation] PGE2 Regulates Breast Cancer Proliferation and Osteoblastic RANKL Production in a Part of Bone Metastasis through its Receptor Subtype of EP4.
  • Author(s): Yokoyama S
  • Organizer: American Society For Bone and Mineral Research 2012
  • Place of Presentation: Minneapolis, Minnesota, USA
• [Presentation] Toll-like receptor 2へテロ受容体 (TLR1/2, TLR 2/6) シグナルによる骨吸収亢進のメカニズム
  • Author(s): 松本千穂
  • Organizer: 第30回日本骨代謝学会
  • Place of Presentation: 東京、京王プラザホテル