Development of new strategy for jaw deformity using CNP

• Project/Area Number: 15K20516
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Kyoto University
• Principal Investigator: NAKAO Kazumasa 京都大学, 医学研究科, 助教 (40599932)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: CNP / 顎変形症 / 内軟骨性骨化 / 軟骨無形成症

Outline of Final Research Achievements

Analysis of the μCT image of achondroplasia (Ach) model mice revealed midfacial hypoplasia in the sagittal direction and foramen magnum stenosis similarly to human. Both hypertrophic chondrocyte layers and proliferating chondrocyte layers the cartilage of the skull base of the Ach mice were narrowed, and early ossification with angiogenesis and apoptosis was found in the center of the cartilage of the skull base. The midfacial hypoplasia and the foramen magnum stenosis in the Ach mice could be significantly improved by the increase in the blood concentration of CNP.
It was suggested that administration of CNP could improve the abnormalities of craniofacial morphology found in achondroplasia by promoting endochondral ossification in the cranial cartilage.

Research Products

• [Journal Article] Circulatory CNP Rescues Craniofacial Hypoplasia in Achondroplasia (2017)
  • Author(s): Yamanaka S.、Nakao Kazumasa、Koyama N.、Isobe Y.、Ueda Y.、Kanai Y.、Kondo E.、Fujii T.、Miura M.、Yasoda A.、Nakao Kazuwa、Bessho K.
  • Journal Title: Journal of Dental Research Volume: 96 Issue: 13 Pages: 1526-1534
  • DOI: 10.1177/0022034517716437
  • Peer Reviewed / Open Access
• [Journal Article] A novel therapeutic strategy for midfacial hypoplasia using the CNP/GC-B system. (2017)
  • Author(s): Nakao K, Yasoda A, Okubo Y, Yamanaka S, Koyama N, Osawa K, Isobe Y, Ikeno M, Fujii T, Miura M, Bessho K.
  • Journal Title: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Volume: 29 Issue: 1 Pages: 10-16
  • DOI: 10.1016/j.ajoms.2016.07.007
  • Peer Reviewed
• [Presentation] 軟骨無形成症の顎顔面形態異常発症のメカニズム解析と新規治療法についての検討. (2016)
  • Author(s): 山中茂樹，中尾一祐, 小山典昭, 磯部悠, 別所和久
  • Organizer: 第61回日本口腔外科学会学術集会 2016/11/25-27
  • Place of Presentation: 千葉
  • Year and Date: 2016-11-25
• [Presentation] 軟骨無形成症モデルマウスに生じた顎顔面形態異常に対する、C型ナトリウム利尿ペプチドの有効性について (2015)
  • Author(s): 山中茂樹, 八十田明宏, 中尾一祐, 小山典昭, 藤井寿人, 近藤絵里, 三浦晶子, 稲垣暢也, 別所和久, 中尾一和
  • Organizer: 第33回日本骨代謝学会学術集会
  • Place of Presentation: 東京都
  • Year and Date: 2015-07-23