Molecular Mechanisms in Osteoblast and Osteocyte Related with Drug Induced Osteonecrosis of the Jaws

• Project/Area Number: 26861717
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Osaka University
• Principal Investigator: MIYAGAWA KAZUAKI 大阪大学, 歯学部附属病院, 医員 (50635381)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 骨細胞 / 骨芽細胞 / ビスフォスフォネート / 抗RANKL抗体 / 顎骨壊死 / 抗 RANKL抗体 / Sclerostin / デノスマブ

Outline of Final Research Achievements

Bisphosphonate (BP) and anti-RANKL antibody are widely used as anti-resorptive agents for bone metastasis and osteoporosis. Although these agents have different effect mechanism, thay can sometimes result in osteonecrosis of the jaw (ONJ). We examined that these agents were different influence for the bone formation by osteocyte and osteoblast in long bones. This was evident in ovariectomized C57BL/6J mice, which were treated with zoledronic acid (ZOL) or anti-RANKL antibody. Bone mass in long bone of both mice groups treated with ZOL and anti-RANKL antibody under lack of estrogen had significantly increased compared to control mice. Additionally, the changes in the expression of bone formation-related genes (Sost, Dmp1, and Osteocalcin) in long bones of mice treated with either ZOL or anti-RANKL antibody was different. Thus, these results suggested that the regulatory mechanisms of bone formation in osteocytes and osteoblasts differs between BP and anti-RANKL antibody.

Research Products

• [Journal Article] Extracellular Phosphate Induces the Expression of Dentin Matrix Protein 1 Through the FGF Receptor in Osteoblasts. (2017)
  • Author(s): Nishino J, Yamazaki M, Kawai M et al.
  • Journal Title: J Cell Biochem. Volume: 118 Issue: 5 Pages: 1151-1163
  • DOI: 10.1002/jcb.25742
  • Peer Reviewed
• [Journal Article] Alendronate does not prevent long bone fragility in an inactive rat model. (2016)
  • Author(s): Naruse K, Uchida K, Suto M, Miyagawa K, Kawata A, Urabe K, Takaso M, Itoman M, Mikuni-Takagaki Y
  • Journal Title: J Bone Miner Metab. Volume: 34 Issue: 6 Pages: 1-12
  • DOI: 10.1007/s00774-015-0714-y
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] TGF-β in jaw tumor fluids induces RANKL expression in stromal fibroblasts. (2016)
  • Author(s): Yamada C, Aikawa T, Okuno E, Miyagawa K, Amano K, Takahata S, Kimata M, Okura M, Iida S, Kogo M.
  • Journal Title: International Journal of Oncology Volume: 49 Issue: 2 Pages: 499-508
  • DOI: 10.3892/ijo.2016.3548
  • NAID: 120006349208
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 骨ミネラル代謝制御の司令塔としての骨細胞 (2014)
  • Author(s): 宮川和晃、道上敏美
  • Journal Title: 大阪府立母子保健総合医療センター雑誌 Volume: 30
  • Peer Reviewed
• [Journal Article] Dysregulated gene expression in the primary osteoblasts and osteocytes isolated from hypophosphatemic Hyp mice. (2014)
  • Author(s): Miyagawa K, Yamazaki M, Kawai M, Nishino J, Koshimizu T, Ohata Y, Tachikawa K, Mikuni-Takagaki Y, Kogo M, Ozono K, Michigami T
  • Journal Title: PLoS One Volume: 9 Issue: 4 Pages: 0-0
  • DOI: 10.1371/journal.pone.0093840
  • Peer Reviewed / Open Access
• [Presentation] 下顎頭切除と上下顎移動術の一期的手術の術後安定性 (2017)
  • Author(s): 宮川和晃、相川友直、新宅優子、田中晋、伊藤慎将、三原聖美、足立敏、石濱孝二、原田丈司、内橋俊大、山田早織、高畑惣介、毛利真弥、辻忠孝、山城隆、古郷幹彦
  • Organizer: 第27回顎変形症学会総会・学術大会
• [Presentation] 口腔扁平上皮癌による顎骨進展様式は腫瘍内微小環境により異なる (2017)
  • Author(s): 高畑惣介、相川友直、宮川和晃、自見英治郎、古郷幹彦
  • Organizer: 第35回日本骨代謝学会学術大会
• [Presentation] β-TCPとオトガイ骨混合移植による顎裂部骨移植の骨質評価． (2016)
  • Author(s): 松下豊，宮川和晃，廣石幸恵，田中晋，古郷幹彦．
  • Organizer: 第61回 日本口腔外科学会総会・学術大会
  • Place of Presentation: 幕張メッセ（千葉県千葉市）
  • Year and Date: 2016-11-25
• [Presentation] 下顎骨延長術にて咬合の獲得を得た両側科学頭吸収症例の１例． (2016)
  • Author(s): 宮川和晃，相川友直，足立敏，新宅優子，田中晋，水谷雅英，関壮樹，山田早織，古郷幹彦．
  • Organizer: 第26回 日本顎変形症学会総会・学術総会．
  • Place of Presentation: 学術総合センター（東京都千代田区）
  • Year and Date: 2016-06-24
• [Presentation] Three-dimensional analysis of chin bone for secondary bone graft with beta- TCP in unilateral cleft patients. (2015)
  • Author(s): Miyagawa K, Hiroishi S, Matsushita Y, Tanaka S, Kogo M.
  • Organizer: American Society for Bone and Mineral Research 2015 Annual Meeting
  • Place of Presentation: Seattle, WA, USA
  • Year and Date: 2015-10-09
  • Int'l Joint Research
• [Presentation] 3-dimensional analysis of mandibular bone graft with β-TCP for the cleft patients. (2015)
  • Author(s): Hiroishi S, Miyagawa K, Seikai T, Otsuki K, Tanaka-Isomura E, Tanaka S, Kogo M.
  • Organizer: 10th European Craniofacial Congress
  • Place of Presentation: Gothenburg, Sweden
  • Year and Date: 2015-06-24
  • Int'l Joint Research
• [Presentation] β-TCPを用いた顎裂部オトガイ骨移植術の三次元的評価． (2015)
  • Author(s): 宮川和晃，廣石幸恵，磯村恵美子，大槻浩一，青海哲也，田中晋，古郷幹彦．
  • Organizer: 第39回日本口蓋裂学会・学術集会
  • Place of Presentation: 砂防会館（東京都・千代田区）
  • Year and Date: 2015-05-21
• [Presentation] 歯原性腫瘍の顎骨吸収の分子機序―腫瘍間質線維芽細胞のRANKL発現を軸とした解析― (2014)
  • Author(s): 宮川和晃、相川友直、奥野恵実、山田智明、大倉正也、古郷幹彦
  • Organizer: 第59回公益社団法人日本口腔外科学会総会・学術大会
  • Place of Presentation: 千葉
  • Year and Date: 2014-10-17 – 2014-10-19
• [Presentation] Activation of FGF/FGF Receptor Signaling in the Primary Osteocytes Isolated from Hypophosphatemic Hyp Mice (2014)
  • Author(s): Miyagawa K, Yamazaki M, Kawai M, Nishino J, Koshimizu T, Ohata Y, Tachikawa K, Mikuni-Takagaki Y, Kogo M, Ozono K, Michigami T
  • Organizer: American Society for Bone and Mineral Research 2014 Annual Meeting
  • Place of Presentation: Houston, Texas, USA
  • Year and Date: 2014-09-12 – 2014-09-15