九州大学 研究者情報
論文一覧
森山 泰子(もりやま やすこ) データ更新日:2021.06.29

助教 /  歯学研究院 歯学部門 口腔機能修復学


原著論文
1. Tianren Zhou, Yasuko Moriyama, Yasunori Ayukawa, Yunia Dwi Rakhmatia, Xudiyang Zhou, Jiangqi Hu, Kiyoshi Koyano , Injectable Porous Bioresorbable Composite Containing Fluvastatin for Bone Augmentation, ACS Biomaterials Science & Engineering, https://doi.org/10.1021/acsbiomaterials.9b01045, 5, 10, 5422-5429, 2019.08, The purpose of this study was to evaluate the effects of an injectable composite made up of calcium sulfate (CAS), fluvastatin (FS), and atelocollagen on bone augmentation in rats. Porous structures and compressive strength of composites were evaluated. The cumulative release kinetics of FS were determined in vitro by a spectrophotometer. To observe bone regeneration in vivo, five different materials (normal saline; atelocollagen gel only; composite of CAS and atelocollagen; composite containing 0.5% FS; and composite containing 1.0% FS) were injected in extraction sockets and in the crania of rats. Microcomputed tomography and histological evaluation were performed after 2, 4, and 8 weeks of healing time. The composites had high porosity (greater than 55%). FS kept a slow and stable release for >30 days. In vivo results demonstrated that more new bone was formed in the FS groups compared with the other groups, and both bone mass and bone density had prominent increase in maxillae and crania. Resorption of the composite was also observed for cranial tissues. In conclusion, this composite can be applied percutaneously, without any incision. It has excellent properties with replaceability into bone and anabolic effects for bone formation, as well as a drug delivery system for bone formation..
2. Yoko Takemura, Yasuko Moriyama, Yasunori Ayukawa, Kosaku Kurata, Yunia D. Rakhmatia, Kiyoshi Koyano, Mechanical loading induced osteocyte apoptosis and connexin 43 expression in three‐dimensional cell culture and dental implant model., Journal of Biomedical Materials Research Part A., doi: 10.1002/jbm.a.36597, 107, 4, 815-827, 2019.04.
3. Mikio Imai, Yasunori Ayukawa, Noriyuki Yasunami, Akihiro Furuhashi, Yoko Takemura, Naomi Adachi, Jiangqi Hu, Xudiyang Zhou, Yasuko Moriyama, Ikiru Atsuta, Kosaku Kurata, and Kiyoshi Koyano, Effect of a Single Injection of BenidipineImpregnated Biodegradable Microcarriers on Bone and Gingival Healing at the Tooth Extraction Socket., Advances in Wound Care, doi: 10.1089/wound.2018.0834., 8, 3, 108-117, 2019.03.
4. Haomiao Zhang, Yasuko Moriyama, Yasunori Ayukawa, Yunia Dwi Rakhmatia, Yoko Tomita, Noriyuki Yasunami, Kiyoshi Koyano., Generation and histomorphometric evaluation of a novel fluvastatin-containing poly(lactic-co-glycolic acid) membrane for guided bone regeneration., Odontology, 2018.06, The purpose of this study was to evaluate the effects of a poly(lactic-co-glycolic acid) (PLGA) membrane containing fluvastatin on bone regeneration at bone defects in rat calvaria and tibia for possible use as a guided bone regeneration (GBR) membrane. PLGA and fluvastatin-containing PLGA (PLGA-fluvastatin) membranes were prepared and mechanical properties were evaluated. Standardized bony defects were created in rat calvaria and the right tibia, and covered with a PLGA or PLGA-fluvastatin membrane. Bone regeneration was evaluated using image analysis based on histologic examination. At 4 and 8 weeks after membrane implantation, the PLGA-fluvastatin group displayed enhanced new bone formation around the edge of the defect compared with the PLGA membrane group in the calvarial model. Thick bone regeneration was observed in tibia defect sites in the PLGA-fluvastatin membrane group. These results suggest that the PLGA-containing fluvastatin membrane prepared in this study may potentially be used as a GBR membrane..
5. Urata M, Kokabu S, Matsubara T, Sugiyama G, Nakatomi C, Takeuchi H, Hirata-Tsuchiya S, Aoki K, Tamura Y, Moriyama Y, Ayukawa Y, Matsuda M, Zhang M, Koyano K, Kitamura C, Jimi E., A peptide that blocks the interaction of NF-κB p65subunit with Smad4 enhances BMP-2-induced osteogenesis., Journal of Cellular Physiology, DOI: 10.1002/jcp.26571, 233, 9, 7356-7366, 2018.09.
6. Yasunami Noriyuku, Yasunori Ayukawa, Furuhashi Akihiro, ATSUTA IKIRU, Dwi Rakhmatia Yunia, Moriyama Yasuko, Masuzaki Tomohiro, kiyoshi koyano, Acceleration of hard and soft tissue healing in the oral cavity by a single transmucosal injection of fluvastatin-impregnated poly (lactic-co-glycolic acid) microspheres. An in vitro and rodent in vivo study., Biomedical Materials, 2015.12.
7. ATSUTA IKIRU, Yasunori AYUKAWA, Akihiro Furuhashi, YOICHIRO OGINO, Moriyama Yasuko, Yoshihiro Tsukiyama, kiyoshi koyano, In Vivo and In Vitro Studies of Epithelial Cell Behavior around Titanium Implants with Machined and Rough Surfaces., Clinical Oral Implant Research, 10.1111/cid.12043, 2013.02, Background
The surface roughness of a dental implant affects the epithelial wound healing process and may significantly enhance implant prognosis.
Purpose
We explored the influence of surface roughness on peri-implant epithelium (PIE) sealing and down-growth by comparing machine-surfaced (Ms) and rough-surfaced (Rs) implants.
Materials and Methods
(1) Maxillary first molars were extracted from rats and replaced with Ms or Rs implants. (2) We also compared changes in the morphology of cultured rat oral epithelial cells (OECs) grown on Ms or Rs titanium (Ti) plates.
Results
(1) After 4 weeks, the PIE around Ms and Rs implants showed a similar structure to junctional epithelium (JE). At 16 weeks, Rs implants appeared to form a weak epithelial seal at the tissue-implant interface and exhibited markedly less PIE down-growth than Ms implants but was deeper than that observed in natural teeth. (2) We observed less expression of adhesion proteins in OECs cultured on Rs plates than in cells grown on Ms plates. Additionally, cell adherence, migration, and proliferation on Rs plates were lower, whereas apoptosis was reduced on Ms plates.
Conclusion
Ms implants are a better choice for integration with an epithelial wound healing process..
8. 河野 高志, 鮎川 保則, 森山 泰子, 藏田 耕作, 高松 洋, 古谷野 潔, The effect of low-magnitude, high-frequency vibration stimuli on the bone healing of rat incisor extraction socket.
, Journal of Biomechanical Engineering, 10.1115/1.4007247., 134, 091001-1-091001-6, 2012.09, Effects of small vibration stimuli on bone formation have been reported. In the present study, we used morphological and morphometric procedures to elucidate whether low-magnitude, high-frequency (LMHF) vibration stimuli could enhance the bone healing of rat incisor extraction sockets. After extraction of incisors from six-week-old rats, animals were assigned into a control group and two experimental groups to receive 50 Hz stimuli at either 0.05 mm or 0.2 mm peak-to-peak for an hour/day. LMHF vibration stimuli were generated by placing the mandibles of the animals onto a vibration generator. All groups were subdivided into two, according to the study periods (1 and 3 weeks). After the study period, undecalcified ground sections were taken and morphological and morphometric analyses performed. At both 1 and 3 weeks, newly formed bone was observed mainly in the upper wall of the extraction socket in all groups. Morphometric analyses revealed that the trabecular thickness in both experimental groups at 1 week was significantly greater than that in the control. LMHF vibration stimuli had a positive effect on bone at the early stage of bone healing, particularly in trabecular thickness, at the incisor extraction socket.
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9. Atsuta I, Ayukawa Y, Ogino Y, Moriyama Y, Jinno Y, Koyano K. , Evaluations of epithelial sealing and peri-implant epithelial down-growth around “step-type” implants., Clinical Oral Implant Research, 23, 4, 459-466, 2012.05, Objective: Implant designs that can stimulate and integrate with an epithelial wound-healing process may significantly enhance the efficacy of dental implants. Here, we evaluated the potential of ‘‘step-type’’ implant systems to improve the sealing between the peri-implant epithelium (PIE) and the implant surface, and investigated the effect of implant structure on PIE down-growth.
Materials and methods: Right maxillary first molars were extirpated from rats and implanted with either a straight-type or a step-type implant varying in step height and/or width (Ns: 0.8 mm height, 0.1 mm width; Ws: 0.8 mm height, 0.2 mm width; Hs: 0.4 mm height, 0.1 mm width). Maxillae were harvested at various time points over 16 weeks to evaluate laminin-5 distribution as an indicator
of wound healing and PIE formation, horse-radish peroxidase (HRP) penetration as a measurement of epithelial sealing, and PIE down-growth formation.
Results: In all implant models, the PIE formed from the oral sulcular epithelium and spread apically along the implant surface. In the Ws group, HRP penetration was detected only in the coronal region of the PIE at 4 weeks, whereas in the straight-type, it was observed in the apical region and the connective tissue. At 16 weeks, the Ws implants exhibited markedly less PIE down-growth than the Con, Ns or Hs implants, and were equivalent to that observed in natural teeth.
Conclusion: The step-type implant system may have the potential for improving epithelial sealing at the tissue–implant interface, as well as reducing apical PIE down-growth, thus enhancing dental implant efficacy..
10. Masuzaki Tomohiro, Yasunori AYUKAWA, Moriyama Yasuko, Jinno Yohei, ATSUTA IKIRU, YOICHIRO OGINO, kiyoshi koyano, The effect of a single remote injection of statin-impregnated poly (lactic-co-glycolic acid) microspheres on osteogenesis around titanium implants in rat tibia, Biomaterials, http://dx.doi.org/10.1016/j.biomaterials.2010.01.016, 31, 12, 3327-3334, 2010.04, The aim of this study was to evaluate the effects of newly developed injectable poly (lactic-co-glycolic acid) (PLGA) microspheres containing fluvastatin on osteogenesis around titanium implants in the rat tibia. After confirmation of the sustained-release profile of fluvastatin from the microspheres by an in vitro assay, the microspheres were administered to the back skin of the rats by a single transdermal injection. At 2 and 4 weeks after the implant surgery, the fluvastatin groups showed enhanced new bone formation around the titanium implants without any influence on the serum biochemistry. In addition, the fluvastatin groups showed increased three-point bending strengths of their femurs. The results of this study indicate that a single remote injection of PLGA/fluvastatin microspheres safely and successfully stimulated bone formation around titanium implants and increased the mechanical properties of bone..
11. Yasuko Moriyama, Yasunori Ayukawa, Yoichiro Ogino, Ikiru Atsuta, Mitsugu Todo, Yoshihiro Takao, Kiyoshi Koyano., Local application of fluvastatin improves peri-implant bone quantity and mechanical properties: A rodent study., Acta Biomaterialia, 6, 4, 1610-1618, 2010.04, Statins are known to stimulate osteoblast activity and bone formation. This study examines whether local application of fluvastatin enhances osteogenesis around titanium implants in vivo. Ten-week-old rats received a vehicle gel (propylene glycol alginate (PGA)) or PGA containing fluvastatin (3, 15, 75 or 300 μg) in their tibiae just before insertion of the implants. For both histological and histomorphometric evaluations undecalcified ground sections were obtained and the bone–implant contact (BIC), peri-implant osteoid volume and mineralized bone volume (MBV) were calculated after 1, 2 and 4 weeks. Using the same models mechanical push-in tests were also performed to evaluate the implant fixation strength. After 1 week the MBV and push-in strength were significantly lower in the 300 μg fluvastatin-treated group than in the other groups (P < 0.01). At 2 weeks, however, the BIC and MBV were both significantly higher in the 75 μg fluvastatin-treated group than in the non-fluvastatin-treated groups (P < 0.01). Similar tendencies were observed at week 4. Furthermore, the data showed a good correlation between the MBV and the push-in strength. These results demonstrate positive effects of locally applied fluvastatin on the bone around titanium implants and suggest that this improvement in osseointegration may be attributed to calcification of the peri-implant bone..
12. Yasunori AYUKAWA, YOICHIRO OGINO, Moriyama Yasuko, ATSUTA IKIRU, Jinno Yohei, Kihara Masafumi, Yoshihiro Tsukiyama, kiyoshi koyano, Simvastatin enhances bone formation around titanium implants in rat tibiae, Journal of Oral Rehabilitation, DOI: 10.1111/j.1365-2842.2009.02011.x, 37, 2, 123-130, 2010.02, Summary  Statins are cholesterol-lowering drugs that have been reported to promote bone formation. The purpose of this study was to investigate the effect of simvastatin on the enhancement of bone formation around titanium implants. Thirty-week-old female rats received pure titanium implants in both tibiae. The animals were intra-peritoneally administered 0, 0·125, 1, 5 or 10 mg kg−1 of simvastatin daily. After 30 days, the animals were sacrificed, and specimens were prepared. The bone contact ratio of the implant, bone density in the medullary canal and percentage of cortical bone were obtained. Markers for bone turnover were also measured using sera collected at the time of euthanasia. In the medullary canal, a scanty amount of bone was observed in the 0, 0·125 and 1 mg kg−1 groups. In contrast, in both the 5 and 10 mg kg−1 groups, thicker bone trabeculae were abundant. Histometric observations showed that the bone contact ratio and the bone density of both groups were significantly greater than those of the other groups (anova, P < 0·01). However, no significant difference in the percentage of cortical bone was found between groups. Serum chemistry showed that statin increased bone formation markers and decreased bone resorption markers. In conclusion, although the dose equivalent to that used in human patients with hypercholesterolemia was not effective, a simvastatin dose of 5 mg kg−1 or higher increased medullary bone formation around the titanium. In contrast, no effect of simvastatin on pre-existing cortical bone was indicated..
13. Yasuko MORIYAMA, Yasunori AYUKAWA, Kenichi KABAMURA, Yasuyuki MATSUSHITA, Masafumi KIHARA, Yoshihiro TSUKIYAMA,Mitugu TODO, Yoshihiro TAKAO, Kiyoshi KOYANO, The Alternation of Peri-Implant Bone Response Exposed to Static Lateral Load, Journal of Biomechanical Science and Engineering , 4, 3, 326-335, 2009.07.
14. Yasunori AYUKAWA, Eisuke Yasukawa, Moriyama Yasuko, YOICHIRO OGINO, Hiroko Wada, ATSUTA IKIRU, kiyoshi koyano, Local application of statin promotes bone repair through the suppression of osteoclasts and the enhancement of osteoblasts at bone-healing sites in rats, Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, http://dx.doi.org/10.1016/j.tripleo.2008.07.013, 107, 3, 336-342, 2009.03, Objective
We investigated whether the local administration of simvastatin affected both the cellular events and the bone formation at surgically created bone defects in rat.

Study design
Simvastatin (or a vehicle) was injected into a rat bony defect for 3 consecutive days from the day of surgery. Five or ten days after the injection, new bone tissue was collected, and the gene expressions of bone-related proteins were examined. For the histomorphometry, new bone area was measured.

Results
At day 5, the statin group demonstrated significantly larger new bone area. The number of tartrate-resistant acid phosphatase–positive multinucleated cells in the statin group was less than in the control group. In the statin group, the expressions of both alkaline phosphatase and bone morphogenetic protein 2 mRNA significantly increased. In contrast, the expression of cathepsin K was significantly suppressed in the statin group. Although the levels of both RANK and osteoprotegerin were not affected by statin, the expression of RANKL was depressed. At day 10, there were no significant differences among the groups in either histomorphometric or reverse-transcription polymerase chain reaction analyses.

Conclusion
New bone area increased under the influence of simvastatin; however, the effect did not continue when the administration was terminated. Osteoclast suppression may be the consequence of RANKL depression..
15. Yasuko Moriyama, Yasunori Ayukawa, Yoichiro Ogino, Ikiru Atsuta, Kiyoshi Koyano, Topical application of statin affects bone healing around implants, Clinical Oral Implants Research, 19, 600-605, 2008.01.

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