Elucidation of bone formation signal aimed at the development of medical treatment of osteoporosis induced by deterioration of bone formation

• Project/Area Number: 22590656
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General internal medicine (including Psychosomatic medicine)
• Research Institution: Shimane University
• Principal Investigator: SUGIMOTO Toshitsugu 島根大学, 医学部, 教授 (00226458)
• Co-Investigator(Kenkyū-buntansha): YAMAUCHI Mika 島根大学, 医学部, 講師 (40379681)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 老年医学 / 骨粗鬆症 / 骨形成 / 骨芽細胞 / 副甲状腺ホルモン / 骨形成因子 / Tmem119 / 小胞体ストレス / 筋芽細胞 / 終末糖化産物 / Smad3 / Wnt / βカテニン / カルシウム感知受容体 / ストロンチウム / MAPキナーゼ

Research Abstract

We demonstrated that strontium exhibited anabolic action on bone partly through activating calcium-sensing receptor. We identified a smad3-related factor, Tmem119, which is induced by parathyroid hormone(PTH) and promotes osteoblast differentiation partly via Wnt signal and cross-talk with bone morphogenetic protein-Runx2 pathway. Endoplasmic reticulum stress pathway is involved in the differentiation of myoblasts into osteoblasts enhanced by Tmem119. Advanced glycation end-products inhibits osteoblast differentiation via the suppression of this pathway.

Research Products

• [Journal Article] Vertebral fracture risk after once-weekly teriparatide injection-follow-up study of teriparatide once-weekly efficacy research (TOWER) trial (2013)
  • Author(s): Sugimoto T, Shiraki M, Nakano T, Kishimoto H, Ito M, Fukunaga M, Hagino H, Sone T, Kuroda T, Nakamura T
  • Journal Title: Curr Med Res Opin Volume: 29 Pages: 195-203
  • Peer Reviewed
• [Journal Article] Effects of a single injection of teriparatide on bone turnover barkers in postmenopausal women (2012)
  • Author(s): Shiraki M, Sugimoto T, Nakamura T
  • Journal Title: Osteoporos Int Volume: 24 Pages: 219-226
  • Peer Reviewed
• [Journal Article] Smad7 inhibits differentiation and mineralization of mouse osteoblastic cells (2012)
  • Author(s): Yano M, Inoue Y, Tobimatsu T, Hendy GN, Canaff L, Sugimoto T, Seino S, Kaji H
  • Journal Title: Endocr J Volume: 59(8) Pages: 653-662
  • NAID: 10031064548
  • Peer Reviewed
• [Journal Article] Role of osteoglycin in the linkage between muscle and bone (2012)
  • Author(s): Tanaka K, Matsumoto E, Higashimaki Y, Katagiri T, Sugimoto T, Seino S, Kaji H
  • Journal Title: J Biol Chem Volume: 287(15) Pages: 11616-11628
  • Peer Reviewed
• [Journal Article] Randomized teriparatide [human parathyroid hormone(PTH)1-34]once-weekly efficacy research (TOWER)trial for examining the reduction in new vertebral fractures in subjects with primary osteoporosis and high fracture risk (2012)
  • Author(s): Nakamura T, Sugimoto T, Nakano T, Kishimoto H, Ito M, Fukunaga H, Hagino H, SoneT, Yoshikawa H, Nishizawa Y, Fujita T, Shiraki M
  • Journal Title: J Clin Endicrinol Metab Volume: 97(9) Pages: 3097-3106
  • NAID: 120006985510
  • 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, Inoue Y, Hendy GN, Canaff L, Katagiri T, Kitazawa R, Komori T, Sugimoto T, Seino S, Kaji H
  • Journal Title: Bone Volume: 51 Pages: 158-167
  • Peer Reviewed
• [Journal Article] Decreased PTH levels accompanied by low bone formation is associated with vertebral fractures in postmenopausal women with type 2 diabetes (2012)
  • Author(s): Yamamoto M, Yamaguchi T, Nawata K, Yamauchi M, Sugimoto T
  • Journal Title: J Clin Endocrinol Metab Volume: 97 Pages: 1277-1284
  • Peer Reviewed
• [Journal Article] FAM5C is a soluble osteoblast differentiation factor linking muscle to bone (2012)
  • Author(s): Tanaka K, Matsumoto E, Higashimaki Y, Sugimoto T, Seino S, Kaji H
  • Journal Title: Biochem Biophys Res Commun Volume: 418 Pages: 134-139
  • Peer Reviewed
• [Journal Article] Smad7 inhibits differentiation and mineralization of mouse osteoblastic cells (2012)
  • Author(s): Yano M et al
  • Journal Title: Endocr J Volume: 59 Pages: 653-662
  • Peer Reviewed
• [Journal Article] Advanced glycation end-products(AGEs), but not high glucose, inhibits the osteoblastic differentiation of mouse stromal ST2 cells through the suppression of osterix expression (2012)
  • Author(s): Okazaki K et al
  • Journal Title: Calcif Tissue Int Volume: 91 Pages: 286-296
  • Peer Reviewed
• [Journal Article] Kaji H Novel parathyroid hormone-responsive smad3-related factor, Tmem119,promotes osteoblast differentiation (2011)
  • Author(s): Hisa I, Inoue Y, Hendy GN, Canafi L, Kitazawa R, Kitazawa S, Komori T, Sugimoto T, Seino S
  • Journal Title: J Biol Chem Volume: 286(11) Pages: 9787-9796
  • Peer Reviewed
• [Journal Article] Novel PTH-responsive Smad3-related factor, Tmem119 promotes osteoblast differentiation (2011)
  • Author(s): Hisa I, et al
  • Journal Title: J Biol Chem Volume: 286 Pages: 9787-9796
  • Peer Reviewed
• [Journal Article] Comparison of serum sclerostin levels among patients with postmenopausal osteoporosis, prmnary hyperparathyroidism and osteomalacia (2011)
  • Author(s): Kaji H, et al
  • Journal Title: Exp Clin Endocrinol Diabetes Volume: 119 Pages: 440-444
  • Peer Reviewed
• [Journal Article] The calcium-sensing receptor (CaR) is involved in strontium ranelate-induced osteoblast differentiation and mineralization. (2010)
  • Author(s): Takaoka S, Yamaguchi T, Yano S, Yamauchi M, Sugimoto T
  • Journal Title: Horm Metab Res Volume: 42 Pages: 627-631
  • Peer Reviewed
• [Journal Article] Fasudil hydrochrolide induces osteoblastic differentiation of stromal cell lines, C3H10T1/2 and ST2, via bone morphogenetic protein-2 expression (2010)
  • Author(s): Kanazawa I, Yamaguchi T, Yano S, Yamauchi M, Sugimoto T
  • Journal Title: Endocr J Volume: 57(5) Pages: 415-421
  • Peer Reviewed
• [Journal Article] Fasudil hydrochloride induces osteoblastic differentiation of stromal cell lines, C3H10T1/2 and ST2 via BMP-2 expression (2010)
  • Author(s): Kanazawa I, et al
  • Journal Title: Endocr J Volume: 57 Pages: 415-421
  • Peer Reviewed
• [Journal Article] Effect of teriparatide on BMD and bone turnover markers in Japanese subjects with osteoporosis at high risk of fracture (2010)
  • Author(s): Miyauchi A, et al
  • Journal Title: Bone Volume: 47 Pages: 493-502
  • Peer Reviewed
• [Journal Article] The calcium-sensing receptor is involved in strontium ranelate-induced osteoblast differentiation and mineralization
  • Author(s): Takaoka S, et al
  • Journal Title: Horm Metab Res Volume: (in press)
  • Peer Reviewed
• [Presentation] 骨粗鬆症新規治療薬:テリパラチド (2012)
  • Author(s): 杉本利嗣
  • Organizer: 第30回日本骨代謝学会
  • Place of Presentation: 東京・京王プラザホテル
  • Year and Date: 2012-07-20
• [Presentation] 骨・カルシウム代謝異常とPTH (2012)
  • Author(s): 杉本利嗣
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋・名古屋国際会議場
  • Year and Date: 2012-04-19
• [Presentation] 骨粗鬆症治療の進歩 (2012)
  • Author(s): 杉本利嗣
  • Organizer: 第109回日本内科学会総会・講演会
  • Place of Presentation: 京都・みやこメッセ
  • Year and Date: 2012-04-13
• [Presentation] 骨・カルシウム代謝異常とPTH (2012)
  • Author(s): 杉本 利嗣
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Invited
• [Presentation] 新規骨粗鬆症治療薬 PTH (2011)
  • Author(s): 杉本利嗣
  • Organizer: 第29回日本骨代謝学会学術集
  • Place of Presentation: 大阪・大阪国際会議場
  • Year and Date: 2011-07-28
• [Presentation] 新規骨粗鬆症治療薬:PTH (2011)
  • Author(s): 杉本利嗣
  • Organizer: 第29回日本骨代謝学会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2011-07-28
• [Presentation] 骨形成促進剤としてのPTHの臨床応用への展開 (2010)
  • Author(s): 杉本利嗣
  • Organizer: 第28回日本骨代謝学会
  • Place of Presentation: 東京・京王プラザホテル
  • Year and Date: 2010-07-21
• [Presentation] 骨形成促進剤としてのPTHの臨床応用への展開 (2010)
  • Author(s): 杉本利嗣
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-21
• [Book] 先制医療 日本の未来を拓く医療:治療医学から先制医療へ:骨粗鬆症 (2012)
  • Author(s): 杉本利嗣
  • Publisher: 診断と治療社
• [Book] 先制医療 日本の未来を拓く医療：治療医学から先制医療へ 骨粗鬆症 (2012)
  • Author(s): 杉本 利嗣
  • Publisher: 診断と治療社