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Hisashi Shinoda

Publications and source records attributed to Hisashi Shinoda.

15 recordsLinked to original sources

Effects of lactation on alveolar bone loss in experimental periodontitis.

BACKGROUND: The development and progression of periodontitis are accelerated by various systemic conditions. The present study was designed to determine whether lactation affects alveolar bone loss in rat models of experimental periodontitis. METHODS: Sixty-two female Wistar rats were bred with male rats and divided into three groups that were fed diets containing 0.9%, 0.3%, and 0.02% calcium. They were divided further into two subgroups of lactating and non-lactating animals. An elastic ring was placed around the neck of the right mandibular first molar to induce periodontitis (experimental side) on day 32 after mating. The left first molar was not fitted with an elastic ring (control side). After the lactation period, bone mineral density (BMD) was determined, and a histologic examination of the interdental alveolar bone was performed. RESULTS: On the experimental and control sides, BMD decreased significantly according to the amount of calcium in the diet; however, the magnitude of this decrease was much greater in the lactating group. Histologic examination revealed that in lactating and non-lactating rats, the decrease in BMD was accompanied by a decrease in alveolar bone height on the experimental side, whereas similar results were not seen on the control side. CONCLUSIONS: Lactation could be a risk factor for alveolar bone loss, especially under conditions of calcium insufficiency. Increased systemic demand for calcium and an insufficient supply of calcium might enhance the development of alveolar bone loss in periodontitis.

Alveolar Bone Loss↗

Current topics in pharmacological research on bone metabolism: inhibitory effects of bisphosphonates on the differentiation and activity of osteoclasts.

Despite the extensive use of bisphosphonates (BPs) in the treatment of metabolic bone diseases associated with increased osteoclastic bone resorption, the precise mechanism of their action on bone metabolism is still unclear. To clarify at which stages of osteoclast differentiation and activation that BPs influence, we examined the osteoclasts generated from mononuclear precursors and osteoclasts in the calvaria by laser scanning confocal microscopy. The studies showed that BPs inhibit lipopolysaccharide- or parathyroid hormone-induced osteoclast differentiation, fusion, attachment, actin ring formation, and activation and that both beta3 integrin and osteopontin have an important role in cytoskeletal rearrangements associated with cell attachment and resorption in osteoclasts.

Actins↗

[Application of bisphosphonates for periodontitis].

Bisphosphonates are known as highly effective inhibitors of osteoclastic bone resorption that selectively affect osteoclasts. They are world-wildly used for the treatment of metabolic bone diseases with excessive bone resorption such as osteoporosis and Paget's disease. Alveolar bone loss in periodontitis results from local inflammatory reactions by periodontopathic bacteria. It has been reported that bisphosphonates efficiently prevent experimentally induced alveolar bone resorption in animals with periodontitis, and that bisphosphonate therapy improves the outcome of periodontal treatment in human being. Administration of bisphosphonates may be an appropriate adjunctive treatment to preserve periodontal bone mass. Further studies are needed regarding topical drug delivery system, effective dose and frequency of administration, possible side effects, and which bisphosphonate is suitable for periodontitis.

Animals↗

Osteoclast responses to lipopolysaccharide, parathyroid hormone and bisphosphonates in neonatal murine calvaria analyzed by laser scanning confocal microscopy.

Because the development and activity of osteoclasts in bone remodeling is critically dependent on cell-cell and cell-matrix interactions, we used laser confocal microscopy to study the response of osteoclasts to lipopolysaccharide (LPS; 10 microg/ml), parathyroid hormone (PTH; 10(-8) M), and bisphosphonates (BPs; 1-25 microM clodronate or 0.1-2.5 microM risedronate) in cultured neonatal calvaria. Following treatment with LPS or PTH (<48 hr), osteopontin (OPN) and the alphavbeta3 integrin were found colocalized with the actin ring in the sealing zone of actively resorbing osteoclasts. In contrast, non-resorbing osteoclasts in BP-treated cultures showed morphological abnormalities, including retraction of pseudopods and vacuolization of cytoplasm. In the combined presence of LPS and BP, bone-resorbing osteoclasts were smaller and the sealing zone diffuse, reflecting reduced actin, OPN, and beta3 integrin staining. Depth analyses of calvaria showed that the area of resorbed bone was filled with proliferating osteoblastic cells that stained for alkaline phosphatase, collagen type I, and bone sialoprotein, regardless of the presence of BPs. These studies show that confocal microscopy of neonatal calvaria in culture can be used to assess the cytological relationships between osteoclasts and osteoblastic cells in response to agents that regulate bone remodeling in situ, avoiding systemic effects that can compromise in vivo studies and artifacts associated with studies of isolated osteoclasts.

Acid Phosphatase↗

Effects of local administration of clodronate on orthodontic tooth movement and root resorption in rats.

Clodronate, a non-N-containing bisphosphonate, strongly inhibits bone resorption and also has anti-inflammatory properties. The purpose of this study was to examine the effect of the local administration of clodronate on orthodontic tooth movement. Both the right and left upper first molars of 26 7-week-old male Wistar rats were moved buccally with a standardized expansion spring. Clodronate solution was injected into the sub-periosteum area adjacent to the left upper molar every third day during the experimental period. The right first molar served as the control. Local injection of clodronate caused a significant (P < 0.001) and dose-dependent reduction in tooth movement in the rats. The number of osteoclasts on the clodronate-injected side was significantly less (P < 0.01) than on the control side. Local clodronate also inhibited root resorption incident to tooth movement. These results suggest that localized use of clodronate could be a useful therapeutic adjunct in orthodontic treatment.

Alveolar Process↗

Inhibitory effect of a novel bisphosphonate, TRK-530, on dental calculus formation in rats.

BACKGROUND: A newly developed bisphosphonate, TRK-530 (disodium dihydrogen[4-(methylthio)phenylthio]methanebisphosphonate), has recently been reported to show anti-inflammatory and anti-bone-resorbing activity. Since bisphosphonates have been shown to inhibit the formation of calcium-phosphate crystals in vitro, TRK-530 may inhibit the formation of dental calculus. Therefore, the present study was performed to examine whether this compound has such an effect. METHODS: Three groups of Wistar rats fed a calculogenic diet (RC16) were treated with TRK-530 in drinking water at concentrations of 0 (control group), 0.75, and 1.5 mM. Another group received a daily subcutaneous injection of TRK-530 at a dose of 2.25 micromoles/rat, which was assumed to correspond to the maximum amount of this compound absorbed from the intestine when rats received 1.5 mM TRK-530 in drinking water. Rat dental calculus formation was evaluated. The crystalline nature of dental calculus was studied by x-ray diffraction analysis. Finally, the effects of TRK-530 on the precipitation of calcium-phosphate from solution were tested in vitro. RESULTS: TRK-530 in drinking water inhibited dental calculus formation dose-dependently. However, subcutaneous injection of TRK-530 did not have any significant effect, suggesting that the anticalculus effect of TRK-530 in drinking water was topical, not systemic. The calculus that formed in both the control and experimental groups was primarily hydroxyapatite, a main constituent of human dental calculus. TRK-530 inhibited the precipitation of calcium-phosphate from solution in vitro. CONCLUSIONS: TRK-530 inhibited the formation of dental calculus in a dose-dependent fashion via a local effect. Inhibition of the precipitation of calcium-phosphate from solution might be involved in the anticalculogenic mechanism of this drug.

Administration, Topical↗

Effects of chronic administration of zonisamide, an antiepileptic drug, on bone mineral density and their prevention with alfacalcidol in growing rats.

We investigated the effects of chronic administration of zonisamide, an antiepileptic agent, on bone metabolism in growing rats. Administration of zonisamide at a dose of 80 mg/kg per day, s.c. for 5 weeks significantly decreased bone mineral density (BMD) at the tibial metaphysis and the diaphysis. The percent rate of decrease in BMD at the tibial metaphysis and the tibial diaphysis was 9.2% and 5.0%, respectively. There was no significant difference between these groups in the growth of the rats. Treatment with zonisamide at a dose of 80 mg/kg increased serum pyridinoline level, a marker of bone resorption, while it does not affect the serum intact osteocalcin level, a marker of bone formation. Combined administration of alfacalcidol, an active vitamin D(3) metabolite, at a dose of 0.1 microg/kg per day with zonisamide prevented a decrease in BMD and showed an increase of serum pyridinoline levels. These results suggest that zonisamide may cause bone loss by accelerating bone resorption rather than inhibiting bone formation. Moreover, the bone loss induced by zonisamide could be prevented by combining zonisamide with alfacalcidol.

Animals↗

[Pharmacological actions and pharmacokinetics of bisphosphonates].

Bisphosphonates are potent inhibitors of osteoclastic bone resorption and have been used for the treatment of various metabolic bone diseases such as osteoporosis and hypercalcemia of malignancy. However, the pharmacological action, the mechanism of action, and even side effects vary depending on the chemical structure of the side chain attached to the carbon atom of P-C-P bond. This review discussed about the pharmacological characteristics and possible application of different classes of bisphosphonates with different side chains.

English Abstract↗

[Effects of bisphosphonates on alveolar bone resorption in experimental periodontitis].

Bisphosphonates (BPs) have been successfully used to treat bone diseases such as osteoporosis, Paget's disease of bone, and hypercalcemia of malignancy, which are associated with excessive bone resorption. Periodontitis is also characterized by excessive bone resorption which could lead tooth loss. In this paper, the author described about effects of BPs on alveolar bone resorption in experimental periodontitis, and discussed about the possible use of BPs for the treatment of periodontitis in the clinic.

English Abstract↗

Involvement of nitric oxide in orthodontic tooth movement in rats.

Nitric oxide (NO) is an important regulatory molecule in bone formation and resorption. The purpose of this study was to examine the role of NO in orthodontic tooth movement in rats. We used specific inhibitors of NO synthases (NOS). Upper first molars of 9-week-old male Wistar rats were moved buccally for 21 days. The local administration of N(G)-nitro-L-arginine methyl ester. HCl (L-NAME), a general inhibitor of NOS activity, significantly reduced tooth movement. On the other hand, N(6)-(1-iminoethyl)-L-lysine. 2HCl (L-NIL), a selective inhibitor of the inducible isoform of NOS, had no effect. These results suggest that NO is an important biochemical mediator in the response of periodontal tissue to orthodontic force and is produced primarily through the activity of constitutive NOS.

Analysis of Variance↗

Effects of methylprednisolone on bone formation and resorption in rats.

Excessive glucocorticoids induce osteoporosis. However, there is some controversy regarding the mechanism of action, and even the endpoint result. The present study was carried out to obtain further insight into the action of glucocorticoids on bone formation and resorption in rats. Growing rats were injected subcutaneously with methylprednisolone (mPSL) at doses of 0, 2.5, 5, 10 or 20 mg/kg per day for 4 weeks. Bone mineral density (BMD), enchondral and periosteal bone formation, collagen synthetic activities of osteoblasts, numbers of osteoblasts and osteoclasts, and serum markers to assess bone turnover were determined. Administration of mPSL dose-dependently increased the BMD in the tibial metaphysis, while it dose-dependently decreased the BMD in the diaphysis. Both enchondral and periosteal bone formation were decreased in a dose-dependent fashion. The incorporation and secretion of (3)H-proline by osteoblasts were both decreased in trabecular and cortical bones. The number of osteoclasts, together with the number of osteoblasts, in the tibial metaphysis was drastically decreased. Serum alkaline phosphatase and osteocalcin were decreased at higher doses. These results support the recent notion that glucocorticoids inhibit both bone formation and resorption. In addition, BMD as an endpoint result might differ from site to site in bone due to a different balance between bone formation and resorption.

Adipocytes↗

[Bisphosphonates and adhesion molecules].

Bisphosphonates are highly effective inhibitors of osteoclastic bone resorption. They can be divided into two groups with distinct mechanisms of action. The nitrogen-containing bisphosphonates (pamidronate, alendronate, risedronate, incadronate etc) can inhibit the mevalonate pathway in osteoclasts and inhibit protein prenylation of small G proteins including Rho, which might lead to alter cytoskeletal organization and cell motility. Others, like etidronate and clodronate, do not inhibit protein prenylation and can be incorporated into ATP-containing compounds that may be cytotoxic to osteoclasts. Further studies would be required to elucidate the molecular mechanism of bisphosphonate actions.

English Abstract↗

[Effects of pregnancy, lactation and dietary calcium on alveolar bone loss].

Periodontitis is a local inflammatory disease mainly induced by periodontopathic bacteria including Porphyromonas gingivalis. This disease is characterized by the destruction of periodontal tissues including alveolar bone, which is accelerated by various local and systemic factors. In recent years, many investigators focused on the relationships between periodontitis and systemic diseases such as diabetes and osteoporosis. We are currently studying the effects of pregnancy, lactation and dietary calcium on the bone mineral density of rat alveolus. The results obtained so far showed that pregnancy and subsequent lactation decreased the bone mineral density, and could be the risk factors for alveolar bone loss, especially under the condition of Ca insufficiency or deficiency. Further studies are required to define the relationships between periodontitis and systemic diseases affecting bone metabolism.

English Abstract↗

Preventive effect of ferulic acid on bone loss in ovariectomized rats.

An extract from corn germ induced a positive response in the pigeon crop sack test, used for the detection of prolactin-like substances. One of the substances extracted was identified as ferulic acid, which was reported to affect serum gonadotropin levels in ovariectomized male rats. To evaluate the effects of ferulic acid on bone loss, ovariectomized female rats of the Sprague-Dawley strain at age 35 weeks were given ferulic acid and/or 17a-ethynylestradiol daily for 8 weeks, and serum hormone levels and tibial bone mineral density were measured. In metaphysis of the tibia, which was abundant in cancellous bone and more reflective of BMD than whole tibia, the BMD was markedly reduced by ovariectomy and enhanced by the treatment with estrogen or ferulic acid in the ovariectomized rats. The treatment slightly increased the serum levels of estrogen and progesterone and alkaline phosphatase activity, which was reduced by estrogentreatment, i.e. the mechanism of bone formation by ferulic acid was suggested to be different from that by estrogens. These results indicate that ferulic acid promotes bone remodeling, leading to a predominantly osteoblastic phase, besides bone resorption by osteoclasts.

Animals↗