Role of Osteoclast Extracellular Signal-Regulated Kinase (ERK) in Cell Survival and Maintenance of Cell Polarity

Hiroaki Nakamura, Azumi Hirata, Takehito Tsuji, Toshio Yamamoto

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Morphological changes of osteoclasts by a MEK1 inhibitor, PD98059, were investigated to clarify a role of ERK. PD98059 promoted apoptosis of osteoclasts and the loss of ruffled borders. This study supports the importance of ERK in survival and polarity of osteoclasts. Introduction: Extracellular signal-regulated kinase (ERK) is a mitogen activated protein kinase (MAPK) that has been reported to play a role in the survival and apoptosis of osteoclasts. However, the precise signal transduction mechanism is not fully understood. The aim of this study was to clarify the role of ERK in osteoclasts by histological analysis. Materials and Methods: Using a rat calvarial organ culture system, the inhibition of ERK phosphorylation by PD98059, a MAPK/ERK kinase 1 (MEK1) inhibitor, was assayed by immunoblotting. Morphological changes in osteoclasts induced by PD98059 were elucidated by light and electron microscopy. The cellular localization of ERK was also determined by immunoelectron microscopy. Results: PD98059 inhibited phosphorylated ERK after a 1-h incubation. Ultrastructural study demonstrated that PD98059 induced the accumulation of vesicles and vacuoles in osteoclasts and the loss of ruffled border at 1 h. At 3 h, some osteoclasts showed apoptosis with nuclear condensation, and at 6 h after PD98059 treatment, many osteoclasts were detached from the bone surface and had lost their cell polarity. Electron microscopic immunohistochemistry revealed that ERK was mainly localized in the cytoplasm of clear zones in control osteoclasts, but apoptotic osteoclasts also showed immunoreactivity in clear zone-like structures in contact with osteoblast-lineage cells. Conclusion: These findings indicate that ERK in osteoclasts is involved in their survival and may be involved in the formation of a ruffled border and the maintenance of cell polarity.

Original languageEnglish
Pages (from-to)1198-1205
Number of pages8
JournalJournal of Bone and Mineral Research
Volume18
Issue number7
DOIs
Publication statusPublished - Jul 1 2003

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Cell Polarity
Extracellular Signal-Regulated MAP Kinases
Osteoclasts
Cell Survival
Maintenance
Apoptosis
Mitogen-Activated Protein Kinases
MAP Kinase Kinase 1
Immunoelectron Microscopy
Organ Culture Techniques
Mitogen-Activated Protein Kinase Kinases
Vacuoles
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
Osteoblasts
Immunoblotting
Signal Transduction
Electron Microscopy
Cytoplasm
Phosphotransferases
Immunohistochemistry

Keywords

  • Extracellular signal-regulated kinase
  • Immunohistochemistry
  • Mitogen-activated protein kinase
  • Osteoclasts
  • PD98059

ASJC Scopus subject areas

  • Surgery

Cite this

Role of Osteoclast Extracellular Signal-Regulated Kinase (ERK) in Cell Survival and Maintenance of Cell Polarity. / Nakamura, Hiroaki; Hirata, Azumi; Tsuji, Takehito; Yamamoto, Toshio.

In: Journal of Bone and Mineral Research, Vol. 18, No. 7, 01.07.2003, p. 1198-1205.

Research output: Contribution to journalArticle

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