Investigation of the relationship between bone formation and inflammatory signaling

• Project/Area Number: 25462369
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Research Institute, Osaka Medical Center for Maternal and Child Health (2015); Osaka University (2013)
• Principal Investigator: Higuchi Chikahisa 地方独立行政法人大阪府立病院機構大阪府立母子保健総合医療センター(研究所), その他部局等, その他 (40432421)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: osteoblast / Btk / CRP / MEK5 / MEK1 / MEK2 / 炎症シグナル / MAPK

Outline of Final Research Achievements

We investigated the relationship between inflammatory signaling and osteoblasts. Our data demonstrated that Bruton’s tyrosine kinase(Btk) and C reactive protein(CRP)/FcR signal pathways suppresseed the osteoblastic differentiation. In addition, mitogen-activated protein kinase (MAPK) kinase 5 (MEK5) also suppressed the osteoblastic differentiation.
The results in the present study suggested that small molecules to inhibit these signaling pathways might be candidate agents for the treatment of fracture or bone defect to accelerate bone formation.

Research Products

• [Journal Article] MEK5 suppresses osteoblastic differentiation. (2015)
  • Author(s): Kaneshiro S, Otsuki D, Yoshida K, Yoshikawa H, Higuchi C.
  • Journal Title: Biochem Biophys Res Commun. Volume: 463 Issue: 3 Pages: 241-247
  • DOI: 10.1016/j.bbrc.2015.05.035
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Hyaluronan inhibits BMP-induced osteoblast differentiation. (2015)
  • Author(s): Kaneko K, Higuchi C, Kunugiza Y, Yoshida K, Sakai T, Yoshikawa H, Nakata K.
  • Journal Title: FEBS Lett. Volume: 589 Issue: 4 Pages: 447-454
  • DOI: 10.1016/j.febslet.2014.12.031
  • Peer Reviewed
• [Journal Article] Bruton tyrosine kinase (Btk) suppresses osteoblastic differentiation. (2015)
  • Author(s): Kaneshiro S, Ebina K, Shi K, Yoshida K, Otsuki D, Yoshikawa H, Higuchi C.
  • Journal Title: J Bone Miner Metab. Volume: 33 Issue: 5 Pages: 486-495
  • DOI: 10.1007/s00774-014-0612-8
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Bruton's tyrosine kinase suppresses the osteoblast differentiation (2013)
  • Author(s): Shoichi Kaneshiro, Chikahisa Higuchi, Kousuke Ebina, Kenrin Shi, Hideki Yoshikawa
  • Organizer: 2nd Joint Meeting of the International Bone and Mineral Society and The Japanese Society for Bone and Mineral Research
  • Place of Presentation: Kobe, Japan