Novel function of mTOR in inducing intervertebral disc degeneration

2014 Fiscal Year Final Research Report

• Project/Area Number: 25861303
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: University of Yamanashi
• Principal Investigator: WAKO Masanori 山梨大学, 総合研究部, 助教 (30402077)
• Research Collaborator: HARO Hirotaka 山梨大学, 総合研究部, 教授 (10313264) ; ANDO Takashi 山梨大学, 総合研究部, 助教 (10377492) ; SATO Nobutaka 山梨大学, 総合研究部, 助教 (00418716)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: トロンビン / PAR-1 / MCP-1 / migration

Outline of Final Research Achievements

We herein report various effects of thrombin on mouse osteoblastic MC3T3-E1 cells. MC3T3-E1 cells expressed PAR1, also known as the coagulation factor II receptor. They also produced MCP-1, tissue factor (TF), MCSF and IL-6 upon thrombin stimulation through PI3K-Akt and MEK-Erk1/2 but not the MKK-p38 pathway. Furthermore, MCP-1 obtained from thrombin-stimulated MC3T3-E1 cells induced migration by macrophage RAW264 cells. All these effects of thrombin on MC3T3-E1 cells were abolished by the selective non-peptide thrombin receptor inhibitor SCH79797. We also found that thrombin, PAR-1, MCP-1, TF as well as phosphorylated AKT and p42/44 were significantly expressed at the fracture site of mouse femoral bone. Collectively, thrombin/PAR-1 interaction regulated MCP-1, TF, MCSF and IL-6 production by MC3T3-E1 cells. Furthermore, MCP-1 induced RAW264 cell migration. Thrombin may thus be a novel cytokine that regulates several aspects of osteoblast function and fracture healing.

Free Research Field

骨軟骨代謝