Development of optimally cross-linked collagen scaffold directed to differentiation control of stem cells

• Project/Area Number: 15K15704
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Prosthodontics/ Dental materials science and
• Research Institution: Niigata University
• Principal Investigator: Kaku Masaru 新潟大学, 医歯学系, 准教授 (30547542)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: コラーゲン架橋 / 幹細胞 / 移植担体 / 骨芽細胞 / 間葉系幹細胞 / 架橋阻害剤 / 歯根膜細胞

Outline of Final Research Achievements

This study is based on the idea that control of collagen cross-linking in collagen-based cell transplantation carrier not only changes the mechanical properties of the material but also can promote osteoblast differentiation of mesenchymal stem cells. The aim of this project was to analyze the effect of collagen crosslinking on osteoblast differentiation of mesenchymal stem cells. The addition of a crosslinking inhibitor in the osteoblast culture system under certain conditions has succeeded in selectively reducing collagen crosslinking without affecting the amount of collagen produced. Furthermore, it was revealed that changes in collagen crosslinking affect proliferation, initial adhesion, and osteoblast differentiation of mesenchymal stem cells.

Academic Significance and Societal Importance of the Research Achievements

本研究ではコラーゲン架橋の変化が間葉系幹細胞の骨芽細胞分化に影響を及ぼすことを明らかにした。幹細胞の分化制御には多様な因子が影響を及ぼすことが知られているが、細胞外微小環境としてのコラーゲン、中でもその分子間架橋構造による分化制御は新たな知見である。架橋の変化による幹細胞の分化制御機構は、再生医療に広く使われるコラーゲンを基材とした移植担体や補填材の開発への応用が期待される。

Research Products

• [Int'l Joint Research] Univ. of North Carolina at Chapel Hill(米国)
• [Int'l Joint Research] University of North Carolina/University of Texas at Houston(米国)
• [Int'l Joint Research] University of North Carolina/University of Texas(米国)
• [Int'l Joint Research] University of North Carolina(米国)
• [Journal Article] IFT20 is required for the maintenance of cartilaginous matrix in condylar cartilage (2019)
  • Author(s): Kitami Megumi、Yamaguchi Hiroyuki、Ebina Masayuki、Kaku Masaru、Chen Di、Komatsu Yoshihiro
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 509 Issue: 1 Pages: 222-226
  • DOI: 10.1016/j.bbrc.2018.12.107
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Extracellular matrix with defective collagen cross-linking affects the differentiation of bone cells (2018)
  • Author(s): Ida Takako、Kaku Masaru、Kitami Megumi、Terajima Masahiko、Rosales Rocabado Juan Marcelo、Akiba Yosuke、Nagasawa Masako、Yamauchi Mitsuo、Uoshima Katsumi
  • Journal Title: PLOS ONE Volume: 13 Issue: 9 Pages: 1-18
  • DOI: 10.1371/journal.pone.0204306
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A multi-factorial analysis of bone morphology and fracture strength of rat femur in response to ovariectomy (2018)
  • Author(s): Rosales Rocabado Juan Marcelo、Kaku Masaru、Nozaki Kosuke、Ida Takako、Kitami Megumi、Aoyagi Yujin、Uoshima Katsumi
  • Journal Title: Journal of Orthopaedic Surgery and Research Volume: 13 Issue: 1 Pages: 318-328
  • DOI: 10.1186/s13018-018-1018-4
  • Peer Reviewed / Open Access
• [Journal Article] VWC2 Increases Bone Formation Through Inhibiting Activin Signaling (2018)
  • Author(s): Almehmadi Ahmad、Ohyama Yoshio、Kaku Masaru、Alamoudi Ahmed、Husein Dina、Katafuchi Michitsuna、Mishina Yuji、Mochida Yoshiyuki
  • Journal Title: Calcified Tissue International Volume: 103 Issue: 6 Pages: 663-674
  • DOI: 10.1007/s00223-018-0462-9
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] BRCA1 and BRCA2 tumor suppressors in neural crest cells are essential for craniofacial bone development (2018)
  • Author(s): Kitami Kohei、Kitami Megumi、Kaku Masaru、Wang Bin、Komatsu Yoshihiro
  • Journal Title: PLOS Genetics Volume: 14 Issue: 5 Pages: e1007340-e1007340
  • DOI: 10.1371/journal.pgen.1007340
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An ENU-induced splice site mutation of mouse Col1a1 causing recessive osteogenesis imperfecta and revealing a novel splicing rescue. (2017)
  • Author(s): Tabeta K, Du X, Arimatsu K, Yokoji M, Takahashi N, Amizuka N, Hasegawa T, Crozat K, Maekawa T, Miyauchi S, Matsuda Y, Ida T, Kaku M, Hoebe K, Ohno K, Yoshie H, Yamazaki K, Moresco EMY, Beutler B
  • Journal Title: Sci. Rep. Volume: 7(1) Issue: 1 Pages: 11717-11717
  • DOI: 10.1038/s41598-017-10343-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Functional Diversity of Ciliary Proteins in Bone Development and Disease (2017)
  • Author(s): Kaku M, Komatsu Y
  • Journal Title: Curr Osteoporos Rep Volume: Epub ahead of print Issue: 2 Pages: 96-102
  • DOI: 10.1007/s11914-017-0351-6
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A paradigm shift for bone quality in dentistry: A literature review (2017)
  • Author(s): Kuroshima Shinichiro, Kaku Masaru, Ishimoto Takuya Sasaki Muneteru, Nakano Takayoshi, Sawase Takashi
  • Journal Title: Journal of Prosthodontic Research Volume: 61 Issue: 4 Pages: 353-362
  • DOI: 10.1016/j.jpor.2017.05.006
  • NAID: 130006198474
  • ISSN: 1883-1958, 1883-9207
  • Peer Reviewed / Open Access
• [Journal Article] Recruitment of bone marrow-derived cells to the periodontal ligament via the stromal cell-derived factor- 1/C-X-C chemokine receptor type 4 axis (2017)
  • Author(s): Kaku M, Kitami M, Rosales Rocabado JM, Ida T, Akiba Y, Uoshima K.
  • Journal Title: J Periodont Res Volume: Epub ahead of print Issue: 3 Pages: 617-627
  • DOI: 10.1111/jre.12430
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Prolonged Survival of Transplanted Osteoblastic Cells Does Not Directly Accelerate the Healing of Calvarial Bone Defects. (2016)
  • Author(s): Kitami M, Kaku M, Rocabado JM, Ida T, Akiba N, Uoshima K.
  • Journal Title: J Cell Physiol. Volume: 232 Issue: 9 Pages: 1974-82
  • DOI: 10.1002/jcp.25302
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mechanical Loading Stimulates Expression of Collagen Cross-Linking Associated Enzymes in Periodontal Ligament. (2015)
  • Author(s): Kaku M, Rosales Rocabado JM, Kitami M, Ida T, Akiba Y, Yamauchi M, Uoshima K.
  • Journal Title: J Cell Physiol. Volume: 231(4) Issue: 4 Pages: 926-933
  • DOI: 10.1002/jcp.25184
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant