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Chisato Miyaura

Publications and source records attributed to Chisato Miyaura.

13 recordsLinked to original sources
PubMed2006

Membrane-bound prostaglandin E synthase-1-mediated prostaglandin E2 production by osteoblast plays a critical role in lipopolysaccharide-induced bone loss associated with inflammation.

PGE(2) acts as a potent stimulator of bone resorption in several disorders including osteoarthritis and periodontitis. Three PGE synthases (PGES) were isolated for PGE(2) production, but which PGES has the major role in inflammatory bone resorption is still unclear. In this study, we examined the role of PGE(2) in LPS-induced bone resorption using membrane-bound PGES (mPGES)-1-deficient mice (mPges1(-/-)). In osteoblasts from wild-type mice, PGE(2) production was greatly stimulated by LPS following the expression of cyclooxygenase 2 and mPGES-1 mRNA, whereas no PGE(2) production was found in osteoblasts from mPges1(-/-). LPS administration reduced the bone volume in wild-type femur that was associated with an increased number of osteoclasts. In mPges1(-/-), however, LPS-induced bone loss was reduced. We next examined whether mPGES-1 deficiency could alter the alveolar bone loss in LPS-induced experimental periodontitis. LPS was injected into the lower gingiva and bone mineral density of alveolar bone was measured. LPS induced the loss of alveolar bone in wild-type, but not in mPges1(-/-) mice, suggesting an mPGES-1 deficiency resistant to LPS-induced periodontal bone resorption. To understand the pathway of LPS-induced PGE(2) production in osteoblast, we used C3H/HeJ mice with mutated tlr4. Osteoblasts from C3H/HeJ mice did not respond to LPS, and PGE(2) production was not altered at all. LPS-induced bone loss in the femur was also impaired in C3H/HeJ mice. Thus, LPS binds to TLR4 on osteoblasts that directly induce mPGES-1 expression for PGE(2) synthesis, leading to subsequent bone resorption. Therefore, mPGES-1 may provide a new target for the treatment of inflammatory bone disease.

Animals↗
PubMed2006

Soybean isoflavones preserve bone mass in hindlimb-unloaded mice.

It is well known that skeletal unloading induces bone loss. It has been shown that soybean isoflavones are effective in preventing bone loss in osteoporotic animals. We investigated the ability of isoflavones to protect bone loss induced by hindlimb unloading by using a tail-suspension mouse model. Eight-week-old female mice were divided into five groups: (1) normal housed group (Normal), (2) sham unloaded group fed a control diet (Sham-UL), (3) hindlimb unloaded group fed a control diet (UL-C), (4) hindlimb unloaded group fed a 0.25% isoflavone conjugates diet (UL-ISO 0.25), and (5) hindlimb unloaded group fed a 0.5% isoflavone conjugates diet (UL-ISO 0.5). After 3 weeks, bone mineral density (BMD) of the femur was significantly decreased in UL-C, and this bone loss was prevented by isoflavone treatment. Histomorphometric analysis revealed a decrease in the cancellous bone of the distal femur in the UL-C group, and isoflavone prevented this change. Serum corticosterone increased in the UL-C group, and isoflavones inhibited the elevation. These results suggest that isoflavones might be promising food components that provide protection from bone loss and normalize stress-induced serum corticosterone during skeletal unloading.

Animals↗
PubMed2006

[Bone metabolisms of aromatase-knockout mice in male].

Aromatase converts androgen to estrogen as the sole enzyme that related bone metabolism as well as gonadal-genesis. We previously discovered aromatase-knockout (ArKO) mice showed bone loss that associated with increasing bone resorption was seen in both female and male mice. This is suggesting essential roles of estrogen for bone metabolism in both of gender. When male ArKO mice were orchidectomized (ORX) to induce a complete deficiency of both estrogen and androgen, ORX/ArKO showed severe osteopenia. The complexities for use of estrogen and androgen in bone metabolisms may have distinct or synergistic roles of bone turnover in female and male mice before/after reaching to sexual maturity.

Androgens↗
PubMed2005

Estrogen and androgen play distinct roles in bone turnover in male mice before and after reaching sexual maturity.

Aromatase is the sole enzyme which converts androgen into estrogen. We have reported that aromatase-knockout (ArKO) mice showed bone loss by increased bone resorption not only in female but also in male mice, suggesting essential roles of estrogen in bone metabolism in both sexes. However, loss of testicular androgen by orchidectomy (ORX) could induce bone loss in male mice. To clarify the relationship between estrogen and androgen in bone metabolism in male mice, 7-week-old ArKO mice were orchidectomized (ORX) to induce a double deficiency of estrogen and androgen. Bone loss in ORX/ArKO mice was more severe than that in ORX/wild-type and sham/ArKO mice because of advanced bone resorption, indicating that androgen and estrogen individually regulate bone mass by suppressing bone resorption in male mice after reaching sexual maturity. Cortical bone formation was elevated in sham/ArKO mice, but ORX did not influence cortical bone formation in the adult male mice. To examine the influence of androgen deficiency in weaning stage, 3-week-old wild-type mice were orchidectomized. Four weeks after operation, periosteal bone formation in the femur was markedly reduced in ORX mice. Since cortical bone in the same age of ArKO mice was normal, testicular androgen is indispensable for cortical bone formation especially at puberty in male mice. Therefore, estrogen and androgen may play distinct roles in bone turnover of male mice before and after reaching sexual maturity.

Age Factors↗
PubMed2005

[Possible roles of gene deficient mice as a model of osteoporosis].

Recent technical advance for making of gene modified mice includes gene targeting and transgenic mice are clarify the biological function of its targeted molecules. The evidence from gene modified mice on sex-steroid hormones may contribute to develop clinical drugs for osteoporosis treatment especially. Gene deficient mice of the sole enzyme for estrogen synthesis (aromatase), estrogen receptor and androgen receptor deficient mice have great potential to elucidate further mechanisms of pathogenesis of osteoporosis.

Animals↗
PubMed2004

Critical roles for collagenase-3 (Mmp13) in development of growth plate cartilage and in endochondral ossification.

Collagenase-3 (MMP13), a member of the matrix metalloproteinase (MMP) family of neutral endopeptidases, is expressed in the skeleton during embryonic development and is highly overexpressed in human carcinomas and in chondrocytes and synovial cells in rheumatoid arthritis and osteoarthritis. To determine the functional roles of Mmp13, we generated Mmp13-null mice that showed profound defects in growth plate cartilage with markedly increased hypertrophic domains as well as delay in endochondral ossification and formation and vascularization of primary ossification centers. Absence of Mmp13 resulted in significant interstitial collagen accumulation due, in part, to the lack of appropriate collagenase-mediated cleavage that normally occurs in growth plates and primary ossification centers. Cartilaginous growth plate abnormalities persisted in adult mice and phenocopied defects observed in human hereditary chondrodysplasias. Our findings demonstrate a unique role of Mmp13 in skeletal development.

Animals↗
PubMed2004

[LPS].

Explore the source record for details and available documents.

Animals↗
PubMed2003

An essential role of cytosolic phospholipase A2alpha in prostaglandin E2-mediated bone resorption associated with inflammation.

Prostaglandin E (PGE)2 produced by osteoblasts acts as a potent stimulator of bone resorption. Inflammatory bone loss is accompanied by osteoclast formation induced by bone-resorbing cytokines, but the mechanism of PGE2 production and bone resorption in vivo is not fully understood. Using cytosolic phospholipase A2alpha (cPLA2alpha)-null mice, we examined the role of cPLA2alpha in PGE2 synthesis and bone resorption. In bone marrow cultures, interleukin (IL)-1 markedly stimulated PGE2 production and osteoclast formation in wild-type mice, but not in cPLA2alpha-null mice. Osteoblastic bone marrow stromal cells induced the expression of cyclooxygenase (COX)-2 and membrane-bound PGE2 synthase (mPGES) in response to IL-1 and lipopolysaccharide (LPS) to produce PGE2. Osteoblastic stromal cells collected from cPLA2alpha-null mice also induced the expression of COX-2 and mPGES by IL-1 and LPS, but could not produce PGE2 due to the lack of arachidonic acid release. LPS administration to wild-type mice reduced femoral bone mineral density by increased bone resorption. In cPLA2alpha-null mice, however, LPS-induced bone loss could not be observed at all. Here, we show that cPLA2alpha plays a key role in PGE production by osteoblasts and in osteoclastic bone resorption, and suggest a new approach to inflammatory bone disease by inhibiting cPLA2alpha.

Animals↗
PubMed2003

Role of prostaglandin E produced by osteoblasts in osteolysis due to bone metastasis.

Prostaglandin E2 (PGE2) is produced in bone mainly by osteoblasts and stimulates bone resorption. Osteolytic bone metastasis of cancers is accompanied by bone resorption. In this study, we examined the roles of PGE2 in osteolysis due to bone metastasis of breast cancer. Injection of human breast cancer cells, MDA-MB-231 (MDA-231), into nude mice causes severe osteolysis in the femur and tibia. The expression of cyclo-oxygenase-2 (COX-2) and the receptor activator of NF-kappaB ligand (RANKL), a key molecule in osteoclast differentiation, mRNAs was markedly elevated in bone with metastasis. When MDA-231 cells were cocultured with mouse calvaria, COX-2-induced PGE2 production and bone resorption progressed. The contact with MDA-231 cells could induce the expression of COX-2 and RANKL in osteoblasts by mechanisms involving MAP kinase and NF-kappaB. The blockage of PGE2 signal by indomethacin and EP4 antagonist abrogated the osteoclast formation induced by the breast cancer cells. Here, we show a PGE-dependent mechanism of osteolysis due to bone metastasis.

Animals↗
PubMed2003

[Bone metabolism in aromatase-knockout mice].

Aromatase is the sole enzyme which converts androgen into estrogen. We have reported that aromatase-knockout (ArKO) mice showed bone loss by increased bone resorption not only in female but also in male mice, suggesting essential roles of estrogen in bone metabolism in both sexes. When ArKO mice were orchidectomized (ORX) to induce a double deficiency of estrogen and androgen, ORX/ArKO mice showed severe osteopenia. In females, estrogen is major sex steroid for bone turnover. However, estrogen and androgen may play distinct roles in bone turnover of male mice before and after reaching sexual maturity.

English Abstract↗
PubMed2002

Dietary bisphenol A prevents ovarian degeneration and bone loss in female mice lacking the aromatase gene (Cyp19 ).

We previously generated mice lacking aromatase activity by targeted disruption of Cyp19 (ArKO mice), and reported phenotypes of the female mice, showing hemorrhage formation and follicular depletion in the ovary, diminution in uterine size, and bone loss. In the present study, we examined the influence of dietary bisphenol A (BPA), a monomer used for the production of polycarbonate and known to have estrogenic activity, on these phenotypes of the ArKO mice. When ArKO mice were fed chow diets supplemented with 0.1% or 1% (w/w) BPA for 5 months, they were protected from ovarian degeneration, uterine diminution and bone loss in a dose-dependent manner. Northern blot analyses of ovarian RNA of ArKO mice showed differences in the expression levels of insulin-like growth factor (IGF)-I, IGF-I receptor, growth differentiation factor 9 and bone morphogenetic protein 15 as compared with those in the ovaries of wild-type mice. The differences in the expression levels were restored by dietary BPA. In the ArKO uteri, expression of progesterone receptor and vascular endothelial growth factor mRNAs was diminished, and was restored by BPA to the levels in wild-type mice. In contrast, BPA had little effect on the ovarian, uterine and skeletal structures of wild-type mice. In conclusion, estrogenic effects of BPA on the reproductive tract as well as skeletal tissue were evident in adult female ArKO mice. These results suggest that the ArKO mouse is an animal model suitable for studying effects of estrogenic chemicals as well as estrogen in vivo.

Animals↗