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2002 Fiscal Year Final Research Report Summary

Change in epidermal growth factor receptor induced in osteoblastic cells by mechanical stimuli and its role.

Research Project

Project/Area Number 13671493
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionTokyo Medical and Dental University

Principal Investigator

OGATA Toshiko  Tokyo Med. & Dent. Univ., Medical Research Institute, Assistant, 難治疾患研究所, 助手 (80014314)

Project Period (FY) 2001 – 2002
Keywordsmechanical stress / osteoblast / EGF / EGF receptor / leupeptin / endosome / proteolysis / tyrosine-phosphorylation
Research Abstract

It is well documented that mechanical stimuli are essential to maintain homeostasis of bone, and osteoblasts can sense the mechanical stimuli. However, the mechanism to transduce the mechanical stimuli to the intracellular signals have not been elucidated yet. We have found that in a culture system of osteoblast-like cells ERK1/2, She and other proteins are tyrosine-phosphorylated by medium flow and egr-1 mRNA increases. Furthermore, these responses were not induced without serum and recovered by the addition of EGF. These findings suggested that EGF signaling is involved in the responses to mechanical stimuli. Moreover, as there were also reports from other researchers that growth factor receptors were activated by mechanical stimuli, we examined whether activation of EGF receptor is also induced in our system. Although the examination of tyrosine-phosphorylation of the EGF receptor did not lead to significant results, during the experiments we noticed that EGF receptor protein increased after medium flow. This increase was induced within 2 minutes of the stimuli. This rapid response suggested that this increase is induced by rather a decrease in the degradation than an increase in the synthesis. Therefore, we examined the effects to the increase by the several inhibitors for the pathways involved in the proteolysis of EGF receptor. The results showed that the protease inhibitor, leupeptin, blocked the increase. Furthermore, the leupeptin sensitive protease might be cathepsin B was deduced. Cathepsin B is reported to degrade EGF receptor in early endosomes and EGF receptor in early endosome is occupied by EGF. This co-localization of the EGF-occupied EGF receptor and the protease might be the reason for our finding that the increase in EGF receptor by medium flow did not occur without EGF in culture media.

  • Research Products

    (2 results)

All Other

All Publications (2 results)

  • [Publications] Toshiko Ogata: "Increase in epidermal growth factor receptor protein induced in osteoblastic cells after exposure to flow of culture media"American Journal of Physiology : Cell Physiology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toshiko Ogata: "Increase in epidermal growth factor receptor protein induced in osteoblastic cells after exposure to flow of culture media"American Journal of Physiology : Cell Physiology. in press.

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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