The influence of mechanical stress on the gene expression related to the differentiation and the growth of bone cell

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12470433
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Hirosaki University
• Principal Investigator: KIMURA Hiroto Hirosaki University, School of Medicine, Dentistry and Oral Surgery, Professor, 医学部, 教授 (90142851)
• Co-Investigator(Kenkyū-buntansha): SATOH Hisashi Hirosaki University, School of Medicine, Dentistry and Oral Surgery, Assistant, 医学部, 助手 (90311539) ; FUKUI Roh Hirosaki University, Hospital, Dentistry and Oral Surgery, Lecturer, 医学部・附属病院, 講師 (70241479) ; KOBAYASHI Wataru Hirosaki University, School of Medicine, Dentistry and Oral Surgery, Associate professor, 医学部, 助教授 (50234860) ; KUSUMI Akinori Hirosaki University, Hospital, Dentistry and Oral Surgery, Assistant, 医学部・附属病院, 助手 (90332494)
• Project Period (FY): 2000 – 2001
• Keywords: Osteoblast / Mechanical stress / Cyclic tensile strain / Quantitative RT-PCR / Nitric oxide / MAP kinase / sRANKL / Osteoprotegerin

Research Abstract

To study the influence of physical stimulus 6n bone remodeling, using a model of mechanical stress on osteoblasts, we investigated the production of NO and the expression and/or activation of NOS, Cox-2, and MAPKs. Furthermore, the synthesis of receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) were investigated by ELISA.
Results were as follows.
1. Mechanical stress (cyclic tensile strain) against osteoblasts induced the NO production and the expression for iNOS mRNA.
2. By the quantitative RT-PCR method, mechanical stress increased the expression for Cox-2 mRNA. But the expression of mRNA of cytokine and cytokine-receptors were not changed.
3. The p38 MAPK was activated just after starting to add mechanical stress, on the contrary, ERK1/2 and JNK were not activated. Mechanical stress for 3 days, p38 MAPK activation was kept and ERK1/2 activation was down-regulated day by day.
4. Adding mechanical stress at 4 hrs a day for 3days, sRANKL release was decreased and OPG synthesis was increased, simultaneously.
These results suggested that p38 MAPK in osteoblasts was activated by adding mechanical stress. It was revealed consequently that mechanical stress activated osteoblasts to induce NO production, expression for Cox-2 mRNA and OPG through p38 MAPK activation. It was suggested that mechanical stress might enhance the function of osteoblasts to form new bone.