Catecholamine accelerates osteoblastic differentiation by enhancing bone -The effects of exercise on bone formation-

• Project/Area Number: 23592227
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Osaka City University
• Principal Investigator: SUZUKI Akinobu 大阪市立大学, 医学(系)研究科(研究院), 講師 (00445016)
• Co-Investigator(Kenkyū-buntansha): TAKAOKA Kunio 大阪市立大学, 大学院医学研究科, 名誉教授 (30112048) ; HASHIMOTO Yusuke 大阪市立大学, 大学院医学研究科, 講師 (10382178) ; UEMURA Takuya 大阪市立大学, 大学院医学研究科, 病院講師 (10597321)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 骨形成蛋白 / BMP / カテコラミン / 骨代謝 / 骨形成蛋白(BMP) / 骨形成 / 骨形成蛋白（BMP）

Research Abstract

Topical effects of a catecholamine on bone morphogenetic protein (BMP)-induced ectopic bone formation were investigated. Epinephrine enhanced bone induction by BMP-2. The mass of ossicles ectopically induced by BMP-2 was increased by the systemic addition of epinephrine. The expression level of alkaline phosphatase (ALP) in cells was consistently elevated by BMP-2 and was further elevated by the addition of epinephrine. The epinephrine-enhanced ALP elevation was specifically abolished by an antagonist to beta 2-adrenergic receptors and by a protein kinase A inhibitor. The luciferase activity of the Id1 gene was elevated by BMP-2 treatment and this activity was further enhanced by the addition of epinephrine. Epinephrine-enhanced luciferase activity was abolished by mutation of the cAMP-response element (CRE) sequence in the Id1 promoter, indicating that CRE-binding transcription proteins induced by epinephrine addition may act as enhancers of Smad-mediated BMP signaling.

Research Products

• [Journal Article] Prevalence and motion characteristics of degenerative cervical spondylolisthesis in the symptomatic adult (2013)
  • Author(s): Suzuki A, Daubs MD, Inoue H, Hayashi T, Aghdasi B, Montgomery SR, Ruangchainikom M, Hu X, Lee CJ, Wang CJ, Wang BJ, Nakamura H
  • Journal Title: Spine Volume: 38(17)
  • Peer Reviewed
• [Journal Article] The role of internal fixation for long bone metastasis prior to impending fracture : an experimental model (2013)
  • Author(s): Ibrahim M, Terai H, Yamada K, Suzuki A, Toyoda H, Nakamura H
  • Journal Title: J Orthop Sci Volume: 18(4) Pages: 659-66
  • Peer Reviewed
• [Journal Article] Radiographic evaluation of postoperative bone regrowth after microscopic bilateral decompression via a unilateral approach for degenerative lumbar spondylolisthesis (2013)
  • Author(s): Dohzono S, Matsumura A, Terai H, Toyoda H, Suzuki A, Nakamura H
  • Journal Title: J Neurosurg Spine Volume: 18(5) Pages: 472-8
  • Peer Reviewed
• [Journal Article] Impact of initial conservative treatment interventions on the outcomes of patients with osteoporotic vertebral fractures (2013)
  • Author(s): Hoshino M, Tsujio T, Terai H, Namikawa T, Kato M, Matsumura A, Suzuki A, Takayama K, Takaoka K, Nakamura H
  • Journal Title: Spine Volume: 38(11)
  • Peer Reviewed
• [Journal Article] Characteristics of diabetes associated with poor improvements in clinical outcomes after lumbar spine surgery (2013)
  • Author(s): Takahashi S, Suzuki A, Toyoda H, Terai H, Dohzono S, Yamada K, Matsumoto T, Yasuda H, Tsukiyama K, Shinohara Y, Ibrahim M, Nakamura H
  • Journal Title: Spine Volume: 38(6) Pages: 516-22
  • NAID: 10031169974
  • Peer Reviewed
• [Journal Article] Radiographic evaluation of segmental motion of scoliotic wedging segment in degenerative lumbar scoliosis (2013)
  • Author(s): Yasuda H, Matsumura A, Terai H, Toyoda H, Suzuki A, Dozono S, Nakamura H
  • Journal Title: J Spinal Disord Tech Volume: 26(7) Pages: 379-84
  • Peer Reviewed
• [Journal Article] BMP-2 Adverse Reactions Treated With Human Dose Equivalent Dexamethasone in a Rodent Model of Soft-Tissue Inflammation (2013)
  • Author(s): Xiong C, Daubs MD, Montgomery SR, Aghdasi B, Inoue H, Tian H, Suzuki A, Tan Y, Hayashi T, Ruangchainikom M, Chai T, Corey M, Wang JC
  • Journal Title: Spine Volume: 38(19) Pages: 1640-7
  • Peer Reviewed
• [Journal Article] Anterior Opening Wedge Osteotomy of the Proximal Tibia for Genu Recurvatum Caused by Partial Proximal Tibial Epiphyseal Arrest (2013)
  • Author(s): Hara Y, Hashimoto Y, Takigami J, Yamasaki S and Nakamura H
  • Journal Title: Journal of Case Reports in Medicine Volume: Vol2 (ID 235710)
  • Peer Reviewed
• [Journal Article] 円板状半月手術後再手術に至った症例検討 (2013)
  • Author(s): 橋本祐介, 山崎真哉, 瀧上順誠, 寺井彰三郎, 中村博亮
  • Journal Title: JOSKAS(1884-8842) Volume: 38巻1号 Pages: 172-173
  • NAID: 10031162468
  • Peer Reviewed
• [Journal Article] 若年者円板状半月損傷に対する半月形成と縫合併用手術後MRIの経時的変 (2013)
  • Author(s): 橋本祐介, 山崎真哉, 瀧上順誠, 寺井彰三郎, 中村博亮
  • Journal Title: JOSKAS(1884-8842) Volume: 38巻1号 Pages: 170-171
  • Peer Reviewed
• [Journal Article] Radial artery perforator adiposal flap for coverage of the scarred median nerve (2013)
  • Author(s): Uemura T, Takamatsu K, Okada M, Ikeda M, Nakamura H
  • Journal Title: J Plast Reconstr Aesthet Surg Volume: 66(7) Pages: 1019-21
  • Peer Reviewed
• [Journal Article] 末梢神経の再生医療生体吸収性人工神経を用いたiPS cell- & bFGF drug-delivery systemの有効性 (2013)
  • Author(s): 上村卓也, 高松聖仁, 池田幹則, 岡田充弘, 香月憲一, 田畑泰彦, 筏義人, 中村博亮
  • Journal Title: 末梢神経 Volume: 24(1) Pages: 90-8
  • Peer Reviewed
• [Journal Article] Radial artery perforator adiposal flap for coverage of the scarred median nerve. (2013)
  • Author(s): Uemura T, Takamatsu K, Okada M, Ikeda M, Nakamura H.
  • Journal Title: J Plast Reconstr Aesthet Surg Volume: 66(7) Pages: 1019-1021
  • DOI: 10.1016/j.bjps.2013.01.024
  • Peer Reviewed
• [Journal Article] Prevalence and motion characteristics of degenerative cervical spondylolisthesis in the symptomatic adult. (2013)
  • Author(s): Suzuki A, Daubs MD, Inoue H, Hayashi T, Aghdasi B, Montgomery SR, Ruangchainikom M, Hu X, Lee CJ, Wang CJ, Wang BJ, Nakamura H.
  • Journal Title: Spine (Phila Pa 1976). Volume: 38(17) Pages: 1115-1120
  • DOI: 10.1097/brs.0b013e31829b1487
  • Peer Reviewed
• [Journal Article] The role of internal fixation for long bone metastasis prior to impending fracture: an experimental model. (2013)
  • Author(s): Ibrahim M, Terai H, Yamada K, Suzuki A, Toyoda H, Nakamura H.
  • Journal Title: Journal of Orthopaedic Science Volume: 18(4) Pages: 659-666
  • DOI: 10.1007/s00776-013-0380-7
  • Peer Reviewed
• [Journal Article] Radiographic evaluation of postoperative bone regrowth after microscopic bilateral decompression via a unilateral approach for degenerative lumbar spondylolisthesis. (2013)
  • Author(s): Dohzono S, Matsumura A, Terai H, Toyoda H, Suzuki A, Nakamura H.
  • Journal Title: J Neurosurg Spine. Volume: 18(5) Pages: 472-478
  • DOI: 10.3171/2013.2.spine12633
  • Peer Reviewed
• [Journal Article] Impact of initial conservative treatment interventions on the outcomes of patients with osteoporotic vertebral fractures. (2013)
  • Author(s): Hoshino M, Tsujio T, Terai H, Namikawa T, Kato M, Matsumura A, Suzuki A, Takayama K, Takaoka K, Nakamura H.
  • Journal Title: Spine (Phila Pa 1976). Volume: 38(11) Pages: 641-648
  • DOI: 10.1097/brs.0b013e31828ced9d
  • Peer Reviewed
• [Journal Article] Characteristics of diabetes associated with poor improvements in clinical outcomes after lumbar spine surgery. (2013)
  • Author(s): Takahashi S, Suzuki A, Toyoda H, Terai H, Dohzono S, Yamada K, Matsumoto T, Yasuda H, Tsukiyama K, Shinohara Y, Ibrahim M, Nakamura H.
  • Journal Title: Spine (Phila Pa 1976). Volume: 38(6) Pages: 516-522
  • DOI: 10.1097/brs.0b013e318273583a
  • NAID: 10031169974
  • Peer Reviewed
• [Journal Article] Radiographic evaluation of segmental motion of scoliotic wedging segment in degenerative lumbar scoliosis. (2013)
  • Author(s): Yasuda H, Matsumura A, Terai H, Toyoda H, Suzuki A, Dozono S, Nakamura H.
  • Journal Title: J Spinal Disord Tech. Volume: 26(7) Pages: 379-384
  • DOI: 10.1097/bsd.0b013e31824a4129
  • Peer Reviewed
• [Journal Article] Transplantation of induced pluripotent stem cell-derived neurospheres for peripheral nerve repair. (2012)
  • Author(s): Uemura T, Takamatsu K, Ikeda M, Okada M, Kazuki K, Ikada Y, Nakamura H
  • Journal Title: Biochem Biophys Res Commun Volume: 419 Pages: 130-135
  • DOI: 10.1016/j.bbrc.2012.01.154
  • Peer Reviewed
• [Journal Article] Regenerative Repair of Bone Defect with Osteoinductive Hydroxyapatite Fabricated to Match the Defect and Implanted with Combined Use of Computer-aided Design, Computer-aided Manufacturing, and Computer-assisted Surgery Systems : A Feasibility Study in a Canine Model (2012)
  • Author(s): Koichi Yano, Takashi Namikawa, Takuya Uemura, Masatoshi Hoshino, Shigeyuki Wakitani, Kunio Takaoka, Hiroaki Nakamura
  • Journal Title: J Orthop Sci Volume: 17(In press) Pages: 484-489
  • DOI: 10.1007/s00776-012-0235-7
  • Peer Reviewed
• [Journal Article] Bone morphogenetic protein-2 retained in synthetic polymer/β-tricalcium phosphate composite promotes hypertrophy of a vascularized long bone graft in rabbits. (2011)
  • Author(s): Okada M, Yano K, Namikawa T, Uemura T, Hoshino M, Kazuki K, Takaoka K, Nakamura H
  • Journal Title: Plastic and Reconstructive Surgery Volume: 127 Pages: 98-106
  • Peer Reviewed
• [Presentation] Magnetic Resonance Classification System of Cervical Intervertebral Disc Degeneration–Its Validity and Meaning (2013)
  • Author(s): Suzuki A, Daubs MD, Hayashi T, Ruangchainikom M, Xiong C, Scott TP, Phan K, Wang JC
  • Organizer: 第41回Cervical Spine Research Society
• [Presentation] 日本ジュニアエリートテニス選手の世代別障害発生率の検討 (2013)
  • Author(s): 橋本祐介, 米谷泰一, 奥平修三, 平松久仁彦, 中田研
  • Organizer: 第23回日本臨床スポーツ医学会
• [Presentation] 若年性外側完全円板状半月に対する半月術後離断性骨軟骨炎発生率の検討 (2013)
  • Author(s): 橋本祐介, 山崎真哉, 瀧上順誠, 寺井彰三郎, 金田国一, 富原朋弘, 中村博亮
  • Organizer: 第23回日本臨床スポーツ医学会
• [Presentation] iPS細胞ハイブリッド型人工神経による末梢神経再生 (2013)
  • Author(s): 上村卓也、高松聖仁、池田幹則、岡田充弘、田畑泰彦、筏義人、中村博亮
  • Organizer: 第28回日本整形外科学会基礎学術集会
• [Presentation] Acceleration of peripheral nerve regeneration using nerve conduits in combination with induced pluripotent stem cell technology and a basic fibroblast growth factor drug delivery system (2013)
  • Author(s): Uemura T, Takamatsu K, Ikeda M, Okada M, Kazuki K, Nakamura H
  • Organizer: 第68回American Society For Surgery Of The Hand
• [Presentation] Radial artery perforator adiposal flap for the treatment of recurrent adhesion neuropathy of the median nerve (2013)
  • Author(s): Uemura T, Takamatsu K, Okada M, Ikeda M, Kazuki K, Nakamura H
  • Organizer: 第68回American Society For Surgery Of The Hand
• [Presentation] 自家神経移植に匹敵する人工神経の開発iPS細胞とFGF-DDSを導入した新規ハイブリッド型人工神経 (2013)
  • Author(s): 上村卓也、高松聖仁、池田幹則、岡田充弘、田畑泰彦、筏義人、香月憲一、中村博亮
  • Organizer: 第40回日本マイクロサージャリー学会学術集会
• [Presentation] 若年性外側円板状半月に対する半月術後離断性骨軟骨炎発生率の検討 (2013)
  • Author(s): 橋本祐介, 瀧上順誠, 山崎真哉, 寺井彰三郎, 金田国一, 富原朋弘, 島田永和, 中村博亮
  • Organizer: 第38回日本整形スポーツ医学会
• [Presentation] 二重束前十字靱帯再建術後MRI評価と前方不安定性の関係 (2013)
  • Author(s): 橋本祐介, 山崎真哉, 瀧上順誠, 寺井彰三郎, 中村博亮
  • Organizer: 第38回日本整形スポーツ医学会
• [Presentation] iPS細胞ハイブリッド型人工神経による末梢神経の再生医療-マウス坐骨神経欠損モデルにおける長期成績と安全性について- (2013)
  • Author(s): 上村卓也、高松聖仁、池田幹則、岡田充弘、横井卓哉、香月憲一、筏義人、中村博亮
  • Organizer: 第24回日本末梢神経学会学術集会
• [Presentation] Clinical Outcomes of Microsurgical Bilateral Decompression via Unilateral Approach with Midline Spinous Process Splitting for Lumbar Spinal Stenosis–Minimum of 2 years Follow-up– (2013)
  • Author(s): Suzuki A, Terai H, Toyoda H, Takahashi Y, Nakamura H
  • Organizer: 第13回The Pacific and Asian Society of the Minimally Invasive Spine Surgery
• [Presentation] 円板状半月形成術後のMRIを用いた半月形態と内部変化の検討 (2013)
  • Author(s): 橋本祐介, 瀧上順誠, 寺井彰三郎, 中村博亮
  • Organizer: 第5回日本関節鏡・膝・スポーツ整形外科学会
• [Presentation] 二重束前十字靱帯再建術後MRI評価と不安定性の関係 (2013)
  • Author(s): 橋本祐介, 山崎真哉, 瀧上順誠, 寺井彰三郎, 中村博亮
  • Organizer: 第5回日本関節鏡・膝・スポーツ整形外科学会
• [Presentation] Improvement of peripheral nerve regeneration by tissue-engineered nerve conduits combined with induced pluripotent stem cell technology (2013)
  • Author(s): Uemura T, Takamatsu K, Ikeda M, Okada M, Kazuki K, Nakamura H
  • Organizer: 第18回Federation of European Societes for Surgery of the Hand
• [Presentation] 正中神経剥離後に対する橈骨動脈穿通枝脂肪弁の使用経験 (2013)
  • Author(s): 上村卓也、高松聖仁、岡田充弘、池田幹則、中村博亮
  • Organizer: 第86回日本整形外科学会学術集会
• [Presentation] 円板状半月形成術後のMRIを用いた半月形態と内部変化の検討 (2013)
  • Author(s): 橋本祐介, 山崎真哉, 瀧上順誠, 寺井彰三郎, 中村博亮
  • Organizer: 第85回日本整形外科学会学術集会
• [Presentation] Incidence of disc degeneration of the thoracic spine and its effect on the segmental motion and spinal canal in symptomatic patients (2013)
  • Author(s): Suzuki A, Daubs MD, Hayashi T, Aghdasi B, Montgomery SR, Phan K, Scott TP, Nakamura H, Wang JC
  • Organizer: 第40回International Society for the Study of Lumbar Spine
• [Presentation] Wang JC. Prevalence and Motion Characteristics of Degenerative Cervical Spondylolisthesis in Symptomatic Adult (2013)
  • Author(s): Suzuki A, Inoue H, Hayashi T, Nakamura H, Daubs MD
  • Organizer: 第42回日本脊椎脊髄病学会
• [Presentation] Incidence of disc degeneration of the thoracic spine and its effect on the segmental motion and spinal canal in symptomatic patients (2013)
  • Author(s): Suzuki A, Hayashi T, Nakamura H, Daubs MD, Wang JC
  • Organizer: 第42回日本脊椎脊髄病学会
• [Presentation] 正中神経剥離後に対する橈骨動脈穿通枝脂肪弁の有用性 (2013)
  • Author(s): 上村卓也、高松聖仁、岡田充弘、池田幹則、中村博亮
  • Organizer: 第56回日本手外科学会学術集会
• [Presentation] 二重束前十字靱帯再建術後MRI評価と不安定性の関係 (2013)
  • Author(s): 橋本祐介, 瀧上順誠, 山崎真哉, 中村博亮
  • Organizer: 第120回中部日本整形外科災害外科学会
• [Presentation] Transplantation of Induced Pluripotent Stem Cell-derived Neurospheres for Peripheral Nerve Repair (2013)
  • Author(s): Uemura T, Takamatsu K, Ikeda M, Okada M, Nakamura H
  • Organizer: 2013 American Society for Peripheral Nerve
• [Presentation] Prevalence and Motion Characteristics of Degenerative Cervical Spondylolisthesis in Symptomatic Adults (2013)
  • Author(s): Suzuki A, Inoue H, Hayashi T, Nakamura H, Daubs MD, Wang JC
  • Organizer: 第42回日本脊椎脊髄病学会学術集会
  • Place of Presentation: 宜野湾市 沖縄コンベンションセンター
• [Presentation] Incidence of disc degeneration of the thoracic spine and its effect on the segmental motion and spinal canal in symptomatic patients (2013)
  • Author(s): Suzuki A, Hayashi T, Nakamura H, Daubs MD, Wang JC
  • Organizer: 第42回日本脊椎脊髄病学会学術集会
  • Place of Presentation: 宜野湾市 沖縄コンベンションセンター
• [Presentation] Incidence of disc degeneration of the thoracic spine and its effect on the segmental motion and spinal canal in symptomatic patients (2013)
  • Author(s): Suzuki A, Daubs MD, Hayashi T, Aghdasi B, Montgomery SR, Phan K, Scott TP, Nakamura H, Wang JC
  • Organizer: International Society for the Study of Lumbar Spine 2013
  • Place of Presentation: アメリカ、Scottsdale, Fairmont Scottsdale Princess
• [Presentation] Clinical Outcomes of Microsurgical Bilateral Decompression via Unilateral Approach with Midline Spinous Process Splitting (2013)
  • Author(s): Suzuki A, Terai H, Toyoda H, Takahashi Y, Nakamura H
  • Organizer: The Pacific and Asian Society of the Minimally Invasive Spine Surgery 2013
  • Place of Presentation: 日本、宮崎市、PHOENIX SEAGAIA RESORT
• [Presentation] Magnetic Resonance Classification System of Cervical Intervertebral Disc Degeneration; Its Validity and Meaning (2013)
  • Author(s): Suzuki A, Daubs MD, Hayashi T, Ruangchainikom M, Xiong C, Scott TP, Phan K, Wang JC
  • Organizer: Cervical Spine Research Society 2013
  • Place of Presentation: アメリカ、Los Angelees, Hyatt Regency Century Plaza
• [Presentation] iPS細胞ハイブリッド型人工神経による末梢神経の再生医療 -マウス坐骨神経欠損モデルにおける長期成績と安全性について- (2013)
  • Author(s): 上村卓也、高松聖仁、池田幹則、岡田充弘、横井卓哉、香月憲一、筏義人、中村博亮
  • Organizer: 第24回日本末梢神経学会
  • Place of Presentation: 新潟市 朱鷺メッセ
• [Presentation] 自家神経移植に匹敵する人工神経の開発 iPS細胞とFGF-DDSを導入した新規ハイブリッド型人工神経 (2013)
  • Author(s): 上村卓也、高松聖仁、池田幹則、岡田充弘、田畑泰彦、筏義人、香月憲一、中村博亮
  • Organizer: 第40回日本マイクロサージャリー学会
  • Place of Presentation: 盛岡市 盛岡市民文化ホール（マリオス） いわて県民情報交流センター（アイーナ）
• [Presentation] Epinephrine accelerates osteoblastic differentiation by enhancing bone morphogenetic protein signaling through a cAMP/protein kinase A signaling pathway (2012)
  • Author(s): Uemura T, Ohta Y, Nakao Y, Manaka T, Nakamura H, Takaoka K
  • Organizer: SICOT2012
  • Place of Presentation: Dubai, United Arab Emirates, Dubai World Trade Centre
• [Book] ジャンパー膝.今日の治療指針 (2014)
  • Author(s): 橋本祐介
• [Book] 【整形外科領域と再生医療】神経再生iPS細胞と人工神経を用いた末梢神経再生治療開発 (2013)
  • Author(s): 上村卓也, 高松聖仁, 中村博亮
  • Publisher: Pharma Medica (31(4))
• [Book] メディカルレビュー社 (2013)
  • Author(s): 上村 卓也, 高松 聖仁, 中村 博亮
  • Total Pages: 174
  • Publisher: Pharma Medica