Biomedical subjects

Toshio Yamamoto

Publications and source records attributed to Toshio Yamamoto.

22 records · Page 2Linked to original sources

PubMed2003

Role of osteoclast extracellular signal-regulated kinase (ERK) in cell survival and maintenance of cell polarity.

UNLABELLED: 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.

Animals↗

PubMed2003

[Interaction between osteoblasts and osteoclasts].

We reviewed morphological aspects in the interaction between osteoblasts and osteoclasts. Heparan sulfate proteoglycan (HSPG) and fibronectin were localized in the intercellular space between osteoblasts and osteoclasts. HSPG is involved in reservation of growth factors and protection from their proteolysis, suggesting that HSPG may play an important role in cell-cell interaction of bone cells. On the other hand, immunohistochemistry for matrix metalloproteinase (MMP) -13 revealed that MMP-13 produced by osteoblast-lineage cells may play an important role in degradation of type I collagen in bone matrix, acting in concert with cathepsin K and MMP-9 produced by osteoclasts. Bone volume is maintained through the balance of bone formation by osteoblasts and bone resorption by osteoclasts. Their interaction is a critical component of normal bone cell biology.

English Abstract↗

PubMed2002

Evaluation of osteogenic/chondrogenic cellular proliferation and differentiation in the xenogeneic periosteal graft.

To determine whether grafted young periosteum can induce new bone formation in elderly patients, this preliminary study evaluated cell proliferation and differentiation in xenogeneic periosteal grafts in old rats radiographically, histologically, and immunohistochemically. Periosteum harvested from the tibia of young Japanese white rabbits were grafted into old Sprague-Dawley rats with or without administration of 1.0 mg per kilogram per day immunosuppressant FK506. Autogenous old periosteal tissue grafts were also evaluated as a control. Grafted tissue was extirpated after 7, 14, 21, and 45 days. In the xenogeneic group, proliferative cell nuclear antigen-positive cells were observed 7 days after surgery, which differentiated into chondroblasts with bone morphogenetic protein-2 expression and finally formed cartilage by 14 days. Endochondral ossification was observed at 21 days, and bone replacement was completed by 45 days. No osteogenic cell activity was observed in the two other groups. Xenogeneic young periosteum thus maintained its osteogenic/chondrogenic potentiality in older rats.

Age Factors↗

PubMed2002

Localization of osteoprotegerin (OPG) on bone surfaces and cement lines in rat tibia.

Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor (TNF) receptor family, is an osteoclastogenesis inhibitory factor. We investigated the localization of OPG in rat tibia using a specific peptide antibody to clarify the role of OPG in bone remodeling. OPG reactivity was mainly seen on bone surfaces. In bone matrices, OPG was also localized on cartilage/bone interfaces and cement lines. However, labeling was scarcely detected in the region of contact between osteoclasts and stromal cells. Some osteoblasts and osteocytes showed weak labeling. Immunoreactivity was not seen in chondrocytes or osteoclasts. Immunoelectron microscopic observation revealed that OPG is localized on the bone surfaces under osteoclasts. These findings suggest that OPG derived from osteoblast lineage cells and/or serum may be concentrated on resorbed bone surfaces and subsequently on cement lines. OPG may play an important role in the prevention of excess bone resorption by inhibiting differentiation and activity of osteoclasts in bone remodeling.

Animals↗