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Biomedical subjects

Ikuko Ezawa

Publications and source records attributed to Ikuko Ezawa.

11 recordsLinked to original sources

[Osteoporosis and beverage preference].

Opinions regarding beverage preference ingestion and osteoporosis differ with cultural background as well as by eating habits, food customs and other lifestyle factors in addition to climate, differences in each country and area. Furthermore, it is conceivable that it differs with or depends on life stages of the individual. Currently, beverage preferences are enjoyed as part of the eating habits in, daily life considered an indispensable food to be enjoyed thoroughly. Therefore, it may be important to drink a beverage preferences in moderate but not to indulge in excessive ingestion in order to build a healthy lifestyle contributing to both a sound mind and a sound body at each individual life stage.

Beverages↗

Menatetrenone rescues bone loss by improving osteoblast dysfunction in rats immobilized by sciatic neurectomy.

Menatetrenone (MK-4) is a vitamin K2 homologue that has been used as a therapeutic agent for osteoporosis in Japan. However, there is no far any reported evidence that MK-4 ameliorates a pre-existing condition of reduced bone mineral density (BMD) in vivo. In this study, we evaluated the effect of MK-4 in a rat model of established bone loss through immobilization caused by sciatic neurectomy. Unilateral sciatic neurectomy (SNx) was performed in rats, and 10 or 30 mg/kg of MK-4 or vehicle was administered to the rats three weeks after operation. Seven weeks after operation, the rats were sacrificed and BMD and bone histomorphometric parameters were measured to assess the effects of MK-4. While BMD of the distal femoral metaphysis was significantly decreased after SNx, MK-4 administration increased BMD in the neurectomized rats. Bone formation was decreased continuously and bone resorption was initially increased in SNx rats. Four weeks treatment of MK-4 increased bone formation and suppressed bone resorption. In addition, increased carboxylated osteocalcin and decreased undercarboxylated osteocalcin in serum were observed in MK-4-administered rats. These results indicated that MK-4 rescued bone volume by improving osteoblast dysfunction and accelerating gamma carboxylation of osteocalcin. MK-4 may be useful for treating disuse osteopenia.

Animals↗

Enhancement by lactose of intestinal alkaline phosphatase expression in rats.

Lactose promotes the intestinal absorption of calcium independent of the vitamin D endocrine system. This study investigated the effects of lactose on intestinal alkaline phosphatase (ALP) activity in rats. A total of 66 Sprague-Dawley strain female rats (10 weeks old) were divided into two groups: the control and the lactose groups. Animals in the lactose group were fed the experimental diet, in which the 10% of the diet was replaced with lactose. At 0, 3, 7, 14, and 21 days after beginning the experimental diets, rat intestinal segments from the duodenum, jejunum, and ileum were obtained immediately after sacrifice. The segments were slit open longitudinally, and the mucosa was scraped and used for the enzyme assay. The level of intestinal ALP activity in the jejunum from the lactose group was significantly higher than that from the control group. Two kinds of mRNA of rat intestinal ALP (RTIN-1 and RTIN-2) were detected by reverse transcription-polymerase chain reaction (RT-PCR). The level of mRNA expression in the jejunum from the lactose group was enhanced, especially of RTIN-2. This result was compatible with the results of enzymatic activity. These findings suggest that lactose affects intestinal Pi metabolism not only directly, but also in an indirect way via regulation of intestinal ALP expression, especially in the jejunum.

Alkaline Phosphatase↗

[Selection of the supplement in calcium intake].

Adequate calcium intake is one of the most important issues in the prevention and treatment of osteoporosis, which is considered a lifestyle-related disease. However, calcium is a nutrient that is rather difficult to take in appropriate amounts in traditional Japanese eating habits. Therefore, one of the effective means of preventing and treating osteoporosis is to supplement calcium intake, when an insufficient quantity is obtained in the three, daily meals. In addition to increasing the tolerable upper intake levels (UL) of calcium to 2,500 mg/day, and an instruction program for learning how to evaluate the nutritional state, and the right method of utilizing supplements is needed. Furthermore, learning how to balance other nutrients, such as mineral balance, should also be included.

Adolescent↗

Combination use of vitamin K(2) further increases bone volume and ameliorates extremely low turnover bone induced by bisphosphonate therapy in tail-suspension rats.

Bisphosphonate is a potent inhibitor of bone resorption, which results in the increase of bone volume. However, bisphosphonate treatment may lead to extremely low bone turnover and abnormal bone microstructure. In this study, we examined whether the combination of bisphosphonate with vitamin K(2) treatment may have beneficial effects on bone turnover and trabecular microstructure as well as on bone volume loss by using tail-suspension model rats. In these model rats, bone mineral density (BMD) decreased with histological evidence of enhanced bone resorption and suppressed bone formation. By bisphosphonate treatment, BMD was increased compared with that of tail-suspended rats. Osteoclast surface per bone surface (Oc.S/BS) and number of osteoclasts per bone perimeter (N.Oc/B.Pm) were reduced and mineral apposition rate (MAR) decreased, suggesting extreme suppression of bone turnover. However, trabecular structure examined by microfocus CT was apparently abnormal. By contrast, combination of bisphosphonate with vitamin K(2) leads to further increase of bone volume. MAR and BFR as well as Oc.S/BS and N.Oc/B.Pm were increased compared with those of the bisphosphonate-treated group. However, abnormal structure of trabeculae in secondary spongiosa was not completely ameliorated. These data suggested that concomitant use of vitamin K(2) with bisphosphonate excessively ameliorates too much suppression of bone turnover while more efficiently preventing bone volume loss.

Absorptiometry, Photon↗

Menatetrenone ameliorates reduction in bone mineral density and bone strength in sciatic neurectomized rats.

Vitamin K2 (menaquinone) acts on the bone metabolism. Menatetrenon (MK-4) is a vitamin K2 homologue that has been used as a therapeutic agent for osteoporosis in Japan. Rat models of immobilization induced by sciatic neurectomy are characterized by transiently increased bone resorption and sustained reduction in bone formation. Using such a rat model, we investigated the efficacy of MK-4 on bone loss. Male Sprague-Dawley rats were subjected to unilateral sciatic neurectomy and administered MK-4 for 28 d beginning day 21 after operation. The effect of MK-4 on the immobilized bone was assessed by measuring the bone mineral density of the femur, breaking force of the femoral diaphysis, and bone histomorphometry in tibial diaphysis. The BMD on both the femoral distal metaphysis and diaphysis was reduced by sciatic neurectomy. The administration of MK-4 ameliorated this reduction in a dose-dependent manner. The administration of 30 mg/kg MK-4 ameliorated the reduction in bone strength. An improvement in bone formation was observed following the administration of MK-4. These results suggest that MK-4 has a therapeutic potential for immobilization-induced osteopenia.

Absorptiometry, Photon↗

Phosphate depletion enhances bone morphogenetic protein-4 gene expression in a cultured mouse marrow stromal cell line ST2.

Alkaline phosphatases (ALPs) are glycosylated, membrane-bound enzymes that hydrolyze various monophosphate esters at an optimum high pH and are present in nearly all living organisms. In Escherichia coli, extracellular phosphate (Pi) limitation induces the ALP gene, indicating a role of extracellular Pi in ALP gene regulation. However, little is known about similar mechanisms in mammalian cells. Previously, we reported that Pi starvation increased the tissue-nonspecific ALP (TNSALP) activity and regulated its expression in the mouse stromal cell line ST2, derived from mouse bone marrow. In the present study, we further examined the effects of Pi starvation on the mechanism of TNSALP induction. The specific activity of TNSALP increased markedly after treatment by Pi starvation for 5 days and RT-PCR analysis revealed that the mRNA of the bone morphogenetic protein-4 (BMP-4) gene was highly stimulated. The combination of Pi depletion and mouse BMP-4 receptor IA/Fc chimera down-regulated the TNSALP activity. These results indicated that Pi depletion stimulates the TNSALP activity for the Pi supplementation, and that this system may involve the signaling pathway of the BMP-4 gene at the transcription level.

Alkaline Phosphatase↗

Maintenance of trabecular structure and bone volume by vitamin K(2) in mature rats with long-term tail suspension.

Bone volume loss is one of the major health problems during long-term spaceflight. We examined the effects of vitamin K(2) on bone abnormalities in tail-suspended mature male Sprague-Dawley rats (13 weeks old). In this model, increased bone resorption and sustained suppression of bone formation resulted in progressive bone loss in 4 weeks, which simulates bone changes in humans during spaceflight. A significant decrease in bone mineral density (BMD), as well as a decreased mineral apposition rate (MAR), increased number of osteoclasts per bone perimeter (N.Oc/B.Pm), and increased osteoclast surface per bone surface (Oc.S/BS) in the suspended group was effectively prevented by vitamin K(2), given orally (menatetrenone, 22 mg/kg body weight). Microfocus computed tomography (CT) and node-strut analyses revealed that the volume and structure of trabecular bone were maintained near normal by the vitamin K(2) treatment. A recent report has suggested the abnormal metabolism or action of vitamin K in a microgravity environment, and our data therefore suggest that vitamin K(2) may be useful for the prevention of bone loss and for the maintenance of normal trabecular structure during spaceflight.

Absorptiometry, Photon↗

Menatetrenone prevents osteoblast dysfunction in unilateral sciatic neurectomized rats.

Menatetrenone (MK-4) inhibits bone resorption and enhances osteoblast-induced mineralization. In this study, we examined whether MK-4 administration had beneficial effects on osteoblast dysfunction and trabecular microstructure as well as on bone volume loss in a rat model of osteopenia. Male Sprague-Dawley rats were neurectomized and administered MK-4 as a daily supplement. On Day 21 after neurectomy, significant bone loss was observed in the positive control rats. MK-4 prevented the decrease in bone mineral density of the distal metaphysis of the femur. The osteoclast surface per bone surface (Oc.S/BS) and the number of osteoclasts per bone perimeter (N.Oc/B.Pm) were reduced and the mineral apposition rate (MAR) decreased in the immobilized rats on Day 42, suggesting suppression of bone turnover. In contrast, administration with a low dose of menatetrenone led to an increase of MAR and bone formation rate (BFR), while Oc.S/BS and N.Oc/B.Pm remained at normal levels. These data suggested that MK-4 reduced the loss of trabecular bone, prevented osteoblast dysfunction to a certain extent, and contributed to preservation of the trabecular microstructure in this rat model of osteopenia induced by sciatic neurectomy.

Animals↗

The effect of swimming on cartilage formation.

Swimming is a non-weight-bearing exercise. Therefore it has the advantage of maintaining skeletal integrity in aged persons with weakened skeletal structures. Unlike other weight-bearing aerobic exercises, however, it does not appear to exert sufficient stimulus on bone-remodeling activities because the local load-bearing on bone tissues is mild. The purpose of this study was to investigate the effect of swimming on bone remodeling, especially with the use of implanted pellets containing bone morphogenetic protein (BMP) and demineralized bone matrix during the initial stages of the differentiation of mesenchymal cells to cartilage cells. Six-week-old female rats were divided into the swimming group and a control, nonswimming group. Test animals were forced to swim in a water bath for 30 min daily for 2 wk. After the swimming protocol, pellets were implanted and harvested. Messenger RNA isolated from pellets was quantified by means of a reverse transcription-polymerase chain reaction. The expression of RNAs for bone sialoprotein and BMP-6 in pellets from the swimming group was apparently enhanced at 7 d after implantation. These results suggested that systemic hormonal and/or metabolic changes that promote cartilage formation might have occurred after swimming because the effect was observed after the swimming protocol had ended and the pellets were implanted at a non-weight-bearing site.

Animals↗