A5061483064- Bone Metabolism and Diseases
- Bone health and treatments
- Inflammatory mediators and NSAID effects
- Bone health and osteoporosis research
- Estrogen and related hormone effects
- Bone and Dental Protein Studies
- NF-κB Signaling Pathways
- Vitamin D Research Studies
- Growth Hormone and Insulin-like Growth Factors
- Cytokine Signaling Pathways and Interactions
- Alkaline Phosphatase Research Studies
- Cancer, Hypoxia, and Metabolism
- Protein Kinase Regulation and GTPase Signaling
- Fibroblast Growth Factor Research
- Biotin and Related Studies
- Protease and Inhibitor Mechanisms
- Muscle Physiology and Disorders
- Peroxisome Proliferator-Activated Receptors
- Vitamin C and Antioxidants Research
- Bone Tissue Engineering Materials
- Parathyroid Disorders and Treatments
- TGF-β signaling in diseases
- Eicosanoids and Hypertension Pharmacology
- Connective tissue disorders research
- Signaling Pathways in Disease
Meikai University
2003-2020
Eli Lilly (United States)
1997
Nippon Dental University
1997
UConn Health
1993-1996
Taisho Pharmaceutical (Japan)
1994
Tokushima University
1990-1994
Teijin (Japan)
1985-1994
St. Marianna University School of Medicine
1994
Kobe University
1994
Jichi Medical University
1989
Estrogen deficiency causes bone loss, which can be prevented by estrogen replacement therapy. Using a recently developed technique for isolation of highly purified mammalian osteoclasts, we showed that 17 β-estradiol (E2) was able to directly inhibit osteoclastic resorption. At concentrations effective inhibiting resorption, E2 also induced osteoclast apoptosis in dose- and time-dependent manner. ICI164,384 tamoxifen, as pure partial antagonists, respectively, completely or partially blocked...
In bone development and regeneration, angiogenesis bone/cartilage resorption are essential processes closely associated with each other, suggesting a common mediator for these two biological events. To address this interrelationship, we examined the effect of vascular endothelial growth factor (VEGF), most critical angiogenesis, on osteoclastic bone‐resorbing activity in culture highly purified rabbit mature osteoclasts. VEGF caused dose‐ time‐dependent increase area pits excavated by...
Osteoclasts are multinucleate giant cells playing key roles in bone resorption.These solubilize mineralized matrix by means of acid and protease action; however, the precise mechanism this process is not well known.Recently, we succeeded isolation pure osteoclasts from rabbit bones constructed a cDNA library.Using differential screening procedure, two genes expressed predominantly compared with spleen were isolated (Tezuka, K., Sato,
Although the action of insulin-like growth factor-I (IGF-I) on bone formation has been extensively investigated, effect factor resorption is little known. We first examined IGF-I by preexistent osteoclasts using unfractionated cells cultured dentin slices. had a dose-related stimulating osteoclasts, whereas IGF-II did not. When was added to cultures after degenerated slices, increased number osteoclastic multinucleate (MNCs) with tartrate-resistant acid phosphatase activity. Moreover,...
Regulation of mRNA levels for the constitutive and inducible prostaglandin endoperoxide synthases, PGHS-1 PGHS-2, was examined in murine osteoblastic MC3T3-E1 cells. Serum induction PGHS-2 rapid, transient, increased by cycloheximide, inhibited 72% cortisol. The cortisol inhibition blocked cycloheximide. stimulation slower, decreased 28% Increased E2 (PGE2) production immunoreactive protein paralleled changes mRNA. induced at 2 h serum-free cells transforming growth factor-beta (TGF-beta),...
Osteoclasts are multinucleate giant cells that play key roles in bone resorption. To identify genes predominantly expressed osteoclasts, we screened a cDNA library of osteoclasts with probes and alveolar macrophages. Clones specifically hybridizing to the osteoclast probe were isolated sequenced. The nucleotide sequence one such clone, F17, was found share significant similarity sequences human mouse matrix metalloproteinase 9 (MMP-9) cDNA. By isolation sequencing full-length cDNA, F17...
Mechanical loading is crucial for maintenance of bone integrity and architecture, prostaglandins are an important mediator mechanosensing. Cyclooxygenase-2 (COX-2), inducible isoform prostaglandin G/H synthase, induced by mechanical loading-derived fluid shear stress in bone-forming cells such as osteoblasts osteocytes. In this study, we investigated transcription factor transcriptional regulatory elements responsible the stress-induced COX-2 expression osteoblastic MC3T3-E1 cells. When were...
Abstract The effect of prostaglandin E 2 (PGE ) on osteoblastic cell proliferation was investigated using clone MC3T3‐E1 cells cultured in serum‐free medium. PGE at μg/ml increased the number by days after its addition. raised level DNA synthesis a dose‐related fashion constant lag time, maximal being 2–10 and about fourfold over that control 36 hr However, low doses (below 0.2 μg/ml), rather depressed synthesis. Isobutyl methylxanthine counteracted stimulation , forskolin synthesis, which...
Abstract Differentiation of osteoclasts, the cells primarily responsible for bone resorption, is controlled by a variety osteotropic hormones and cytokines. Of these factors, receptor activator NF-κB (RANK) ligand (RANKL) has been recently cloned as an essential inducer osteoclastogenesis in presence M-CSF. Here, we isolated stroma-free population monocyte/macrophage (M/Mφ)-like hemopoietic from mouse unfractionated that were capable differentiating into mature osteoclasts treatment with...
A second prostaglandin G/H synthase (PGHS-2), encoded by a gene separate from that for the original PGHS (PGHS-1), has recently been identified. We have shown PGHS-2 is expressed in cultured mouse calvariae and compared regulation of PGHS-1 messenger RNA (mRNA) levels. mRNA was not detectable freshly isolated bones, but induced during culture further stimulated interleukin-1 (IL-1) PTH. Both factors also increased protein Changes medium E2 (PGE2) production correlated with increases However,...
Vitamin A metabolites such as all-trans-retinoic acid (all-trans-RA) affect several steps of metabolic processes in vertebrates. In the last few years, studies have shown effect RA on bone formation and metabolism. However, mechanisms its action still remain unclear, especially with respect to regulation cells. Therefore, this study was carried out clarify how regulates activity osteoclasts. Using a pit assay involving unfractionated cells, including osteoclasts obtained from rabbits, we...
Bone resorption and the immune system are correlated with each other, both controlled by a variety of common cytokines produced in bone microenvironments. Among these mediators, involvement type I interferons (IFNs) osteoclastic remains unknown. In this study, we investigated participation IFN-beta suppressors cytokine signaling (SOCS)-1 -3 osteoclastogenesis. Addition exogenous to osteoclast progenitors (bone-derived monocytes/macrophages) inhibited their differentiation toward osteoclasts...
Long-term administration of glucocorticoids (GCs) causes osteoporosis with a rapid and severe bone loss slow prolonged disruption. Although the involvement GCs in osteoblastic proliferation differentiation has been studied extensively, their direct action on osteoclasts is still controversial not conclusive. In this study, we investigated participation osteoclastogenesis. Dexamethasone (Dex) at <10–8m stimulated, but >10–7m depressed, receptor activator NF-κB ligand (RANKL)-induced...
The effect of several prostaglandins (PGs) on osteoblastic cells was investigated using clone MC3T3-E1 under serum-free conditions. PGA1, A2, B1, and B2 had little intracellular cAMP, alkaline phosphatase (ALP) activity, DNA synthesis in the cells. At 4–2000 ng/ml, PGE1 among PG analogs tested a dose-dependent stimulatory ALP activity cells, this amplified by isobutyl methylxanthine. Also, strongly augmented amount cAMP over same concentration range. However, PGEj ornithine decarboxylase...
The effects of prostaglandins (PGs) on the induction alkaline phosphatase (ALP) were investigated in osteoblastic clone MC3T3-E1 cells cultured serum-free medium. Prostaglandin E2 (PGE2) stimulated ALP activity a dose-dependent fashion with maximal effect which was about twice that control at concentrations 100-500 ng/ml. Actinomycin D and cycloheximide inhibited stimulative PGE2 cells. PGE2-induced native ALPs same type as adult mouse calvaria, being heat-labile, L-homoarginine-...