Pathogenesis and regenerative therapy of osteoporosis

• Project/Area Number: 26293340
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Mazda Osam 京都府立医科大学, 医学(系)研究科(研究院), 教授 (00271164)
• Co-Investigator(Renkei-kenkyūsha): ARAI Yuji 京都府立医科大学, 医学研究科, 講師 (50347449) ; KITABATAKE Yasuji 大阪大学, 医学系研究科, 助教 (80506494)
• Research Collaborator: KISHIDA Tsunao 京都府立医科大学, 医学研究科, 准教授 (00370205) ; OHGITANI Eriko 京都府立医科大学, 医学研究科, 助教 (80300820) ; WATANABE Eri 京都府立医科大学, 医学研究科, 助教 (20433253) ; SHIN-YA Masaharu 京都府立医科大学, 医学研究科, 助教 (10405277) ; NISHIOKA Keisuke 京都府立医科大学, 医学研究科, 大学院生
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000); Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
• Keywords: 骨粗鬆症 / 骨芽細胞 / 骨・軟骨代謝学

Outline of Final Research Achievements

It is well known that multiple genetic factors are involved in the pathogenesis of osteoporosis. Some SNPs are associated with bone density and the incidence of the osteoporosis. But molecular mechanisms underlying the causative link between the SNPs and bone phenotypes remain to be clarified. We examined influence of some of these SNPs to the differentiation of and signal transduction in osteoblasts, using the direct conversion procedure that reprograms human fibroblasts into osteoblasts. The study may provide insights into the relationship between the SNPs and osteoblast differentiation, leading to understanding of the involvement of genetic factors in the pathogenesis of osteoporosis. The findings may also contribute to establishment of novel tailor-made therapy in the future.

Research Products

• [Journal Article] Direct Conversion of Human Fibroblasts into Schwann Cells that Facilitate Regeneration of Injured Peripheral Nerve In Vivo (2017)
  • Author(s): Sowa Y. et al.
  • Journal Title: Stem Cells Transl Med. Volume: 6 Issue: 4 Pages: 1207-1216
  • DOI: 10.1002/sctm.16-0122
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Suppression of heat shock protein 70 by siRNA enhances the antitumor effects of cisplatin in cultured human osteosarcoma cells (2017)
  • Author(s): Mori Y. et al.
  • Journal Title: Cell Stress Chaperones Volume: in press Issue: 5 Pages: 699-706
  • DOI: 10.1007/s12192-017-0793-x
  • Peer Reviewed
• [Journal Article] Generation of directly converted fuman osteoblasts that are free of exogenous gene and xenogenic protein. (2016)
  • Author(s): Yamamoto K, Sato Y, Honjo K, Ichioka H, Oseko F, Sowa Y, Yamamoto T, Kanamura N, Kishida T, Mazda O.
  • Journal Title: J Cell Biochem Volume: in press Issue: 11 Pages: 2538-45
  • DOI: 10.1002/jcb.25546
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Hypoxia Potentiates Anabolic Effects of Exogenous Hyaluronic Acid in Rat Articular Cartilage (2016)
  • Author(s): Ichimaru S. et al.
  • Journal Title: Int J Mol Sci. Volume: 17 Issue: 7 Pages: 1013-1013
  • DOI: 10.3390/ijms17071013
  • Peer Reviewed / Open Access
• [Journal Article] Direct conversion of human fibroblasts into functional osteoblasts by defined factors (2015)
  • Author(s): Yamamoto K. et al.
  • Journal Title: Proc Natl Acad Sci USA Volume: 112 Issue: 19 Pages: 6152-6157
  • DOI: 10.1073/pnas.1420713112
  • Peer Reviewed
• [Journal Article] Transduction of Oct6 or Oct9 gene concomitant with Myc family gene induced osteoblast-like phenotypic conversion in normal human fibroblast. (2015)
  • Author(s): Mizoshiri N, Kishida T, Yamamoto K, Shirai T, Terauchi R, Tsuchida S, Mori Y, Ejima A, Sato Y, Arai Y, Fujiwara H, Yamamoto T, Kanamura N, Mazda O, Kubo T.
  • Journal Title: Biochem Biophys Res Commun Volume: 467 Issue: 4 Pages: 1110-1116
  • DOI: 10.1016/j.bbrc.2015.10.098
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Femoral perfusion after pulsed electromagnetic field stimulation in a steroid-induced osteonecrosis model (2015)
  • Author(s): Ikegami A et al.
  • Journal Title: Bioelectromagnetics Volume: 未定 Issue: 5 Pages: 349-357
  • DOI: 10.1002/bem.21910
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Hydrostatic Pressure Influences HIF-2 Alpha Expression in Chondrocytes (2015)
  • Author(s): Inoue H et al.
  • Journal Title: Int J Mol Sci Volume: 16 Issue: 1 Pages: 1043-1050
  • DOI: 10.3390/ijms16011043
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Direct conversion of human fibroblasts into functional osteoblasts by defined factors (2015)
  • Author(s): Yamamoto K et al.
  • Journal Title: Proc Natl Acad Sci USA Volume: 未定
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] HIF-1α-induced HSP70 regulates anabolic responses in articular chondrocytes under hypoxic conditions (2014)
  • Author(s): Tsuchida S, Arai Y, Takahashi KA, Kishida T, Terauchi R, Honjo K, Nakagawa S, Inoue H, Ikoma K, Ueshima K, Matsuki T, Mazda O, Kubo T
  • Journal Title: J Orthop Res Volume: (Epub ahead of print) Issue: 8 Pages: 975-980
  • DOI: 10.1002/jor.22623
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/24677016
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of osteoclastogenesis by osteoblast-like cells genetically engineered to produce interleukin-10 (2014)
  • Author(s): Fujioka K et al.
  • Journal Title: Biochem Biophys Res Commun Volume: 456 Issue: 3 Pages: 785-791
  • DOI: 10.1016/j.bbrc.2014.12.040
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 機能的なヒト骨芽細胞のダイレクト・リプログラミング (2015)
  • Author(s): 山本健太、他
  • Organizer: 第36回日本炎症・再生医学会
  • Place of Presentation: 東京
  • Year and Date: 2015-07-21