Yosuke Akiba - Academia.edu (original) (raw)

Papers by Yosuke Akiba

Heredity, 2021

Deformities in cultured fish species may be genetic, and identifying causative genes is essential... more Deformities in cultured fish species may be genetic, and identifying causative genes is essential to expand production and maintain farmed animal welfare. We previously reported a genetic deformity in juvenile red sea bream, designated a transparent phenotype. To identify its causative gene, we conducted genome-wide linkage analysis and identified two single nucleotide polymorphisms (SNP) located on LG23 directly linked to the transparent phenotype. The scaffold on which the two SNPs were located contained two candidate genes, duox and duoxa, which are related to thyroid hormone synthesis. Four missense mutations were found in duox and one in duoxa, with that in duoxa showing perfect association with the transparent phenotype. The mutation of duoxa was suggested to affect the transmembrane structure and thyroid-related traits, including an enlarged thyroid gland and immature erythrocytes, and lower thyroxine (T4) concentrations were observed in the transparent phenotype. The transparent phenotype was rescued by T4 immersion. Loss-of-function of duoxa by CRISPR-Cas9 induced the transparent phenotype in zebrafish. Evidence suggests that the transparent phenotype of juvenile red sea bream is caused by the missense mutation of duoxa and that this mutation disrupts thyroid hormone synthesis. The newly identified missense mutation will contribute to effective selective breeding of red sea bream to purge the causative gene of the undesirable phenotype and improve seed production of red sea bream as well as provide basic information of the mechanisms of thyroid hormones and its related diseases in fish and humans.

Annals of Japan Prosthodontic Society, 2020

Patient: A 52-year-old female complained of masticatory disorder caused by missing mandibular mol... more Patient: A 52-year-old female complained of masticatory disorder caused by missing mandibular molars and esthetic disorder because of malocclusion of the mandibular anterior teeth. After orthodontic treatment, non-vertical stop occlusion and low occlusal vertical dimension were observed. Removable partial dentures and provisional bridges were used to restore the mandibular position. After achieving occlusal support by implants, a porcelain fused to metal crown was made in accordance with the custom incisal table to provide relevant anterior guidance, and occlusal support was acquired by dental implants. Anterior guidance was then reconstructed with the custom incisal table and a porcelain fused to metal crown was fabricated. Discussion: The risk of collapse of occlusion caused by non-vertical stop occlusion was reduced by mandible repositioning and occlusal support by implants. Conclusion: The use of implant prostheses improved the occlusal relationship, esthetics and patient's oral healthrelated quality of life.

PLOS ONE, 2018

Fibrillar type I collagen, the predominant organic component in bone, is stabilized by lysyl oxid... more Fibrillar type I collagen, the predominant organic component in bone, is stabilized by lysyl oxidase (LOX)-initiated covalent intermolecular cross-linking, an important determinant of bone quality. However, the impact of collagen cross-linking on the activity of bone cells and subsequent tissue remodeling is not well understood. In this study, we investigated the effect of collagen cross-linking on bone cellular activities employing a loss-of-function approach, using a potent LOX inhibitor, β-aminopropionitrile (BAPN). Osteoblastic cells (MC3T3-E1) were cultured for 2 weeks in the presence of 0-2 mM BAPN to obtain low cross-linked collagen matrices. The addition of BAPN to the cultures diminished collagen cross-links in a dose-dependent manner and, at 1 mM level, none of the major cross-links were detected without affecting collagen production. After the removal of cellular components from these cultures, MC3T3-E1, osteoclasts (RAW264.7), or mouse primary bone marrow-derived stromal cells (BMSCs) were seeded. MC3T3-E1 cells grown on low crosslink matrices showed increased alkaline phosphatase (ALP) activity. The number of multinucleate tartrate-resistant acid phosphatase (TRAP)-positive cells increased in RAW264.7 cells. Initial adhesion, proliferation, and ALP activity of BMSCs also increased. In the animal experiments, 4-week-old C57BL/6 mice were fed with BAPN-containing diet for 8 weeks. At this point, biochemical analysis of bone demonstrated that collagen cross-links decreased without affecting collagen content. Then, the diet was changed to a control diet to minimize the direct effect of BAPN. At 2 and 4 weeks after the change, histological samples were prepared. Histological examination of femur samples at 4 weeks showed a significant increase in the number of bone surface osteoblasts, while the bone volume and surface osteoclast numbers were not significantly affected. These results clearly demonstrated that the extent of collagen cross-linking of bone matrix affected the differentiation of bone cells, underscoring the importance of collagen cross-linking in the regulation of cell behaviors and tissue remodeling in bone. Characterization of collagen cross-linking in bone may be beneficial to obtain insight into not only bone mechanical property, but also bone cellular activities.

Annals of Japan Prosthodontic Society, 2016

Frontiers in Cell and Developmental Biology, 2014

Bone marrow-derived cells (BMCs) are considered to be a major source of mesenchymal stem cells (M... more Bone marrow-derived cells (BMCs) are considered to be a major source of mesenchymal stem cells (MSCs) in adults and are known to be effective in periodontal tissue regeneration. However, whether endogenous BMCs are involved in periodontal tissue repair process is uncertain. We therefore created periodontal tissue defects in the buccal alveolar bone of mandibular first molars in bone marrow chimeric mice, and immunohistochemically examined the expression of stromal cell derived factor-1 (SDF-1) and the mobilization of BMCs. We found that SDF-1 expression was increased around the defects at as early as 1 week after injury and that BMCs were mobilized to the defects, while GFP+/CD45+ were rarely observed. Fluorescence-activated cell sorting (FACS) analysis demonstrated that the number of platelet-derived growth factor receptor (pdgfr) α+/Sca-1+ (PαS) cells in the bone marrow decreased after injury. Taken together, these results suggest that BMCs are mobilized to the periodontal tissue defects. Recruitment of BMCs, including a subset of MSCs could be a new target of periodontal treatment.

A spatial electrocutaneous display for sensory substitution is being designed. The display will b... more A spatial electrocutaneous display for sensory substitution is being designed. The display will be used to feed back sensory signals from transfemoral prostheses to amputees. The aim is to improve their walking performance. Two experiments have been performed to optimise the display parameters for dynamic, cyclic signals, which are common during walking. From these experiments it became clear that healthy subjects were capable of discerning artificially generated disturbed knee angle patterns from undisturbed patterns. This shows that the electrocutaneous display has the capability to feed back signals from a transfemoral prosthesis.

Cell Communication & Adhesion, 2006

Bone osteoblasts and osteocytes express large amounts of connexin (Cx) 43, the component of gap j... more Bone osteoblasts and osteocytes express large amounts of connexin (Cx) 43, the component of gap junctions and hemichannels. Previous studies have shown that these channels play important roles in regulating biological functions in response to mechanical loading. Here, we characterized the distribution of mRNA and protein of Cx43 in mechanical loading model of tooth movement. The locations of bone formation and resorption have been well defined in this model, which provides unique experimental systems for better understanding of potential roles of Cx43 in bone formation and remodeling under mechanical stimulation. We found that mechanical loading increased Cx43 mRNA expression in osteoblasts and bone lining cells, but not in osteocytes, at both formation and resorption sites. Cx43 protein, however, increased in both osteoblasts and osteocytes in response to loading. Interestingly, the upregulation of Cx43 protein by loading was even more pronounced in osteocytes compared to other bone cells, with an appearance of punctate staining on the cell body and dendritic process. Cx45 was reported to be expressed in several bone cell lines, but here we did not detect the Cx45 protein in the alveolar bone cells. These results further suggest the potential involvement of Cx43-forming gap junctions and hemichannels in the process of mechanically induced bone formation and resorption.

Cancer Letters, 2011

Bone augmentation therapy is used in dental implantation. While techniques to induce bone formati... more Bone augmentation therapy is used in dental implantation. While techniques to induce bone formation are generally successful, the maintenance of bone mass is more difficult. Therefore, it is important to understand the mechanisms that regulate this process. Insulin-like growth factor-1 (IGF-1) is one of the most abundant growth factors that regulate bone mass, promote osteoblast differentiation, and accelerate bone formation. The activity of IGF-1 is regulated by IGF-binding proteins (IGFBPs). IGFBP-3 forms a ternary complex with IGF-1, extending its half-life in the circulating system. Therefore, IGFBP-3 acts as a stabilizer and transporter of IGF-1. Recent studies reported new IGF-1independent functions of IGFBP-3 related with bone metabolism. In this study, we investigated the function of IGFBP-3 in osteoblast differentiation. Our results showed that IGFBP-3 decreases the expression of osteoblast differentiation markers, whose expression is enhanced by bone morphogenetic protein-2 (BMP-2). IGFBP-3 also reduced BMP-2 effect on ALP activity and mineral nodule formation. In addition, IGFBP-3 suppresses the activity of the Smad Binding Element (SBE) reporter, induced by BMP-2 signaling. These results suggest that IGFBP-3 inhibits osteoblast differentiation through the BMP-2 signal pathway, and that IGFBP-3 might play a role in bone mass maintenance in an IGF-1-dependent and-independent manner.

Journal of the European Academy of Dermatology and Venereology, 2019

Metal allergy as a possible cause of Palmoplantar pustulosis (PPP) is a controversial issue, 1-6 ... more Metal allergy as a possible cause of Palmoplantar pustulosis (PPP) is a controversial issue, 1-6 and in particular there is insufficient evidence that removal of dental metal leads to resolution of PPP. This study involved 257 PPP patients (86 males and 171 females, 20-78 years old) who underwent patch testing for metal allergy between 2000 and 2014 at Niigata University Medical and Dental Hospital. Patients who had suffered repeated eruptions of non-infectious pustules on the palms and soles were diagnosed as having PPP. Arthralgia was observed in 21% of the patients and 75.1% (193 patients) had a history of smoking. This article is protected by copyright. All rights reserved.

Background: Sufficient bone quality and quantity are necessary for successful results in a dental... more Background: Sufficient bone quality and quantity are necessary for successful results in a dental implant. Although numerous bone augmentation methods have been reported, used in the clinic and showed successful results in some extent, more reliable methods are still required. Valproic Acid (VPA) which was known as an Antiepilepsy agent and histone deacetylases inhibitor regulate osteoblast differentiation through Runx2 activation in vitro. The present study aimed to evaluate the effects of systemic administration of VPA on bone regeneration in rat maxillary bone cavity. Material and Methods: Fifty-four Wistar rats were used for the experiment. Upper first and second molars were extracted at 4 weeks. Three weeks after extraction, the experimental group received intraperitoneal (IP) injection of VPA and control group received IP injection of saline for 7 days prior to the preparation of bone cavity at the first molar area. Rats were sacrificed on days 3, 7, 14, and 21, and samples we...

Clinical Oral Implants Research

OBJECTIVES Failed implant removal using a high-frequency electrosurgical device (HFED) has been r... more OBJECTIVES Failed implant removal using a high-frequency electrosurgical device (HFED) has been reported to be less invasive than other surgical techniques. We sought to clarify the mechanism of removal torque reduction of an implant by heating with HFED. MATERIALS AND METHODS Sixty-eight Wistar rats received titanium implants on the maxillary bone 4 weeks after extraction of the first and second molars. The control group was sacrificed 6 weeks after implant installation. In the experimental group, the implant was heated by HFED for 10-seconds using three different power outputs, and samples were collected at 3, 7, and 14 days after heating. Removal torque measurement and histological analysis were performed in the control and experimental groups. Implant surfaces were observed using an electron-probe micro analyzer (EPMA). Data were analyzed using Mann-Whitney U-test at a significance level of 5%. RESULTS The removal torque could not be measured in the control group due to fracture of the implant. After heating, the removal torque was measurable without fracture and decreased significantly at 14 days as compared with that at 3 days (p < 0.05). Heating with "min" power output resulted in a significantly smaller blank lacunae area and fewer osteoclasts at 14 days after heating (p < 0.05). EPMA revealed bone matrix adherence to outer surface of heated implant. CONCLUSIONS After heating, an enlarged area of blank lacunae around the implant and an increased number of osteoclasts into the bone marrow cavity were observed, which may have contributed to the reduction in removal torque.

Journal of Prosthodontic Research

Metal alloys have long been used in the dental profession. Although a range of acrylic materials ... more Metal alloys have long been used in the dental profession. Although a range of acrylic materials have been introduced recently, metal alloys are still widely used in dental prostheses. Dental metal allergy refers to the symptoms of contact dermatitis, which is suspected to be associated with the use of metal alloys in dental treatment; however, it does not necessarily reflect a causal relationship. Since being reported in 1928, several clinical, in vitro, and animal studies have investigated its prevalence and etiology[1]. Nevertheless, the cause of dental metal allergy remains poorly understood, despite a recent increase in the number of affected patients in Japan. Although the pathophysiological mechanisms remain unclear, several skin diseases have been suggested to be associated with dental metal alloys, including palmoplantar pustulosis (PPP), dyshidrotic eczema, contact dermatitis, and oral lichen planus[2-6]. Specific types of dermatitis have also been reported to be associated with periodontal disease and apical periodontitis[2,4,7-11]. Studies suggest that the treatment of chronic inflammation, and the replacement of dental metals present in the prostheses may result in the improvement of the skin diseases. This study aimed to determine the relationship between dental metal allergy, PPP, and periodontitis among a group of patients from a dental metal allergy clinic. 2. Materials and Methods 2.1. Patients This study included 436 patients who visited our dental metal allergy clinic between April 1, 2009, and March 31, 2016. All patients provided signed informed consent to participate in the clinical study and to undergo dental treatment, patch testing, and electron probe microanalysis (EPMA). Patients who did not consent to the examination or inclusion in the clinical study, or received a diagnosis that did not require further examination, were excluded. The study protocol was approved by the Research Ethics Committee of our university (2009-5044) and was performed in accordance with the Declaration of Helsinki.

Biochemical and Biophysical Research Communications

Osteoclast and osteoblast are essential for proper bone development and remodeling as well as rec... more Osteoclast and osteoblast are essential for proper bone development and remodeling as well as recovery of bone fracture. In this study, we seek chemical compounds that enhance turnover of bone metabolism for promoting bone healing. First, we screen a chemical library which includes 378 compounds by using murine pre-osteoclastic RAW264.7 cells to identify compounds that promote osteoclastic differentiation. We find that two ROCK (Rho-associated coiled-coil kinase) inhibitors, HA-1077 (Fasudil) and Y-27632, enhance osteoclastogenesis. Subsequently, we identify that these two compounds also increase osteoblastic differentiation of MC3T3-E1 cells. Finally, our in vivo experiment shows that the local administration of ROCK inhibitors accelerate the bone healing of the rat calvarial defect.

Scientific Reports

The micro- and nanosize surface topography of dental implants has been shown to affect the growth... more The micro- and nanosize surface topography of dental implants has been shown to affect the growth of surrounding cells. In this study, standardized and controlled periodic nanopatterns were fabricated with nanosized surface roughness on titanium substrates, and their influence on bone marrow stromal cells investigated. Cell proliferation assays revealed that the bare substrate with a 1.7 nm surface roughness has lower hydrophilicity but higher proliferation ability than that with a 0.6 nm surface roughness. Further, with the latter substrate, directional cell growth was observed for line and groove patterns with a width of 100 nm and a height of 50 or 100 nm, but not for those with a height of 10 or 25 nm. With the smooth substrate, time-lapse microscopic analyses showed that more than 80% of the bone marrow cells on the line and groove pattern with a height of 100 nm grew and divided along the lines. As the nanosized grain structure controls the cell proliferation rate and the nano...

Annals of Japan Prosthodontic Society

Open Journal of Stomatology

Objective: The enhancement of multiple functions, including osteogenesis, angiogenesis, and cell ... more Objective: The enhancement of multiple functions, including osteogenesis, angiogenesis, and cell recruitment, is required for efficient bone regeneration therapy. Recently, special attention has been focused on the microenvironment of stem cells to facilitate bone regeneration. Herein, we examined the effects of various combinations of hypoxic conditions and osteogenic induction on rat mesenchymal cells, to develop a specific protocol for enhancing the multiple cellular functions beneficial to bone regeneration. Methods: Rat mesenchymal cells, isolated from bone marrow, adipose tissue, and periodontal ligament, were examined. The cells were cultured under varied conditions of O 2 tension (hypoxia) and duration and timing of hypoxic exposure, with or without osteogenic induction. Consequently, four different protocols were examined by measuring the gene expression levels of Runx2, Vegfa, and Cxcl12, indicating a capability for osteogenesis, angiogenesis, and cell recruitment, respectively. Finally, the mineralization ability of the rat mesenchymal cells was assessed by quantitating their calcified nodule formation. Results: The simultaneous application of hypoxic exposure and osteogenic induction promoted Vegfa expression in all types of cells, but suppressed Runx2.

International Journal of Developmental Neuroscience, 2013

Defining the molecular mechanisms that underlie development and maintenance of neuronal phenotypi... more Defining the molecular mechanisms that underlie development and maintenance of neuronal phenotypic diversity in the CNS is a fundamental challenge in developmental neurobiology. The vast majority of olfactory bulb (OB) interneurons are GABAergic and this neurotransmitter phenotype is specified in migrating neuroblasts by transcription of either or both glutamic acid decarboxylase 1 (Gad1) and Gad2. A subset of OB interneurons also co-express dopamine, but transcriptional repression of tyrosine hydroxylase (Th) suppresses the dopaminergic phenotype until these neurons terminally differentiate. In mature OB interneurons, GABA and dopamine levels are modulated by odorant-induced synaptic activitydependent regulation of Gad1 and Th transcription. The molecular mechanisms that specify and maintain the GABAergic and dopaminergic phenotypes in the OB are not clearly delineated. In this report, we review previous studies and present novel findings that provide insight into the contribution of epigenetic regulatory mechanisms for controlling expression of these neurotransmitter phenotypes in the OB. We show that HDAC enzymes suppress the dopaminergic phenotype in migrating neuroblasts by repressing Th transcription. In the mature interneurons, both Th and Gad1 transcription levels are modulated by synaptic activity-dependent recruitment of acetylated Histone H3 on both the Th and Gad1 proximal promoters. We also show that HDAC2 has the opposite transcriptional response to odorantinduced synaptic activity when compared to Th and Gad1. These findings suggest that HDAC2 mediates, in part, the activity-dependent chromatin remodeling of the Th and Gad1 proximal promoters in mature OB interneurons.

Journal of Oral and Maxillofacial Surgery, 2014

Purpose: Clinically, bone marrow stromal cells (BMCs) are the most common source of osteoprogenit... more Purpose: Clinically, bone marrow stromal cells (BMCs) are the most common source of osteoprogenitor cells. Its harvest process, however, is invasive to patients. Previous reports have shown the potential advantages of using periosteum-derived cells (PDCs) as a source of cell-based transplant therapy. The objective of our study was to characterize the osteoblastic differentiation and mineralization ability of PDCs versus BMCs and osteoblasts (OBs).