Publications by authors named "Tamayuki Shinomura"

Article Synopsis
  • * Ipriflavone was identified as a potential drug, restoring staining of cartilage cells and increasing extracellular matrix formation in a dose-dependent manner.
  • * In both cell experiments and mouse models of arthritis, Ipriflavone improved symptoms and decreased hyaluronan levels, suggesting it may be an effective treatment for inflammatory arthritis.
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Objective: Few studies have reported on the impact of oxidative stress on the dental implant failure. The aim of this study was to investigate the impact of hyperglycemia-induced oxidative stress on dental implant osseointegration in diabetes mellitus (DM).

Methods: Acid-treated titanium implants were bilaterally placed in the maxillary alveolar ridge of streptozotocin-induced diabetic (DM group) and control rats after extraction of first molars.

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We have previously found and characterized two pairs of enhancer elements, E1 and E2, in the type II collagen alpha 1 chain (COL2A1) gene. Subsequent studies have suggested that these enhancers function differently in the regulation of gene expression. For example, histone deacetylase 10 modifies only the E2 enhancer region to affect gene expression.

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Hyaluronan (HA) has been shown to play crucial roles in the tumorigenicity of malignant tumors. Chondrosarcoma, particularly when low-grade, is characterized by the formation of an extracellular matrix (ECM) containing abundant HA, and its drug/radiation resistance has become a clinically relevant problem. This study aimed to evaluate the effects of a novel hyaluronidase, KIAA1199, on ECM formation as well as antitumor effects on chondrosarcoma.

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To maintain normal function of cartilage tissue normally, the presence of a sufficient amount of type II collagen and aggrecan is essential, and their synthesis is tightly regulated. Therefore, understanding the mechanisms that control the expression of type II collagen and aggrecan would be useful for understanding gene expression changes in diseases such as osteoarthritis. Recently, we have identified two pairs of enhancer elements, termed E1 and E2 in the type II collagen gene and Ea and Eb in the aggrecan gene.

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The endometrium extracellular matrix (ECM) is essential for embryo implantation. Versican, a large chondroitin sulfate proteoglycan that binds hyaluronan and forms large ECM aggregates, can influence fundamental physiological phenomena, such as cell proliferation, adhesion and migration. The present study investigated the possible role of versican in human embryo implantation.

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Hyaluronan (HA) has been shown to play crucial roles in the tumorigenicity of malignant tumors. Chondrosarcoma, particularly when low-grade, is characterized by the formation of an extracellular matrix (ECM) containing abundant HA, and its drug/radiation resistance has become a clinically relevant problem. This study aimed to evaluate the effects of an HA synthesis inhibitor, 4-methylumbelliferone (MU), on ECM formation as well as antitumor effects in chondrosarcoma.

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Context: Sampson's theory cannot explain why only some cycling women develop peritoneal endometriosis. Few studies have focused on the pelvic peritoneum, which receives regurgitated endometrial tissues. We hypothesized that molecular alterations in the peritoneum are involved in the development of peritoneal endometriosis and conducted a microarray analysis to compare macroscopically normal peritoneum sampled from women with peritoneal endometriosis (endometriotic peritoneum) and those without (non-endometriotic peritoneum).

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Article Synopsis
  • The study investigates the localization of three proteins—amelotin (AMTN), odontogenic ameloblast-associated protein (ODAM), and follicular dendritic cell-secreted protein (FDC-SP)—in the junctional epithelium of mice infected with bacteria and inflamed human gum tissue.
  • It was found that while AMTN and FDC-SP expressions were initially stronger in the P. gingivalis infected mice, these levels decreased as inflammation progressed, whereas ODAM levels remained elevated during the inflammation.
  • In human samples, AMTN was consistently present in both inflamed and non-inflamed gums, while ODAM and FDC-SP were more prevalent in healthy tissue but spread into inflamed areas, suggesting these proteins
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Type II collagen is a major component of cartilage, which provide structural stiffness to the tissue. As a sufficient amount of type II collagen is critical for maintaining the biomechanical properties of cartilage, its expression is tightly regulated in chondrocytes. Therefore, it is essential to elucidate in detail the transcriptional mechanism that controls expression of type II collagen, in particular by two enhancer elements we recently discovered.

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Aggrecan is the most abundant proteoglycan in cartilage. It contains a lot of negatively charged glycosaminoglycan chains along the core protein, providing a large osmotic swelling pressure within the cartilage. Therefore, the biomechanical properties of cartilage, such as its compressive load-bearing capacity, are highly dependent on the presence of abundant aggrecan in the cartilage matrix.

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Type II collagen is a major component of cartilage where it is present at a high concentration, which is essential for the functional maintenance of the tissue. Therefore, any fundamental understanding of the physiology of cartilage tissue must include an understanding of the mechanism that allows the high level of expression of type II collagen gene, Col2a1, by chondrocytes. To this end, we developed a new reporter assay system based on the co-transfection of candidate enhancer elements and reporter construct into Swarm rat chondrosarcoma chondrocytes that allowed their stable expression.

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Versican (Vcan)/proteoglycan (PG)-M is a large chondroitin sulfate proteoglycan which forms a proteoglycan/hyaluronan (HA) aggregate in the extracellular matrix (ECM). We tried to generate the Vcan knockout mice by a conventional method, which resulted in mutant mice Vcan(Δ3/Δ3) whose Vcan lacks the A subdomain of the G1 domain. The Vcan knockout embryos died during the early development stage due to heart defects, but some Vcan(Δ3/Δ3) embryos survived through to the neonatal period.

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Background: Heparan sulfate proteoglycans (HSPGs) are one of the basic constituents of plasma membranes. Specific molecular interactions between HSPGs and a number of extracellular ligands have been reported. Mechanisms involved in controlling the localization and abundance of HSPG on specific domains on the cell surface, such as membrane rafts, could play important regulatory roles in signal transduction.

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Versican, a large chondroitin sulfate proteoglycan that binds hyaluronan and is composed of large extracellular matrix aggregates, has been shown to correlate with tumor progression. No studies have examined the roles of versican in chondrosarcoma nor compared them to those of aggrecan. In clinical specimens of human chondromatous tumors, versican expression was significantly increased in malignant tumors, moreover, as the tumor grade increased.

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Study Design: A study of the histologic changes of the intervertebral discs (IVDs) in biglycan (Bgn)-deficient mice.

Objective: In this study, we investigate whether the absence of Bgn accelerates the degenerative process in mouse intervertebral disc (IVD).

Summary Of Background Data: Proteoglycans and collagen fibrils are major components in the extracellular matrix (ECM) composition of IVD.

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There are no data about the expression pattern of activating transcription factor 5 (Atf5) during limb development. The aim of the present study was to describe the expression of Atf5 throughout mouse limb development. Some specimens were examined for the expression of type II collagen alpha1 (Col2a1), sex-determining region Y-related high-mobility-group-box 9 (Sox9), and activating transcription factor 2 (Atf2) by in situ hybridization.

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Follicular dendritic cell-secreted protein (FDC-SP) is a small secretory protein having structural similarities to statherin, a protein in saliva thought to play a role in calcium retention in saliva. In contrast, FDC-SP is thought to play a role in the immune system associated with germinal centers. We report here the very specific expression of FDC-SP in junctional epithelium at the gingival crevice.

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Suppression subtractive hybridization is very effective to enrich differentially expressed genes in two different tissues or cells. We therefore used the technique to identify characteristic genes expressed in rat knee joint articular cartilage as compared to rat costal cartilage. In this study, we revealed that several genes were enriched in a subtracted articular cartilage cDNA library.

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Versican/PG-M is a large chondroitin sulfate proteoglycan of the extracellular matrix with a common domain structure to aggrecan and is present in cartilage at low levels. Here, we characterized cartilage versican during development and growth. Immunostaining showed that versican was mainly localized in the interterritorial zone of the articular surface at 2 weeks in mice, whereas aggrecan was in the pericellular zone of prehypertrophic and hypertrophic cells of the growth plate.

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Molecular understanding of cartilage differentiation has been improved during the past decade. The finding of Sox9 in particular has improved our understanding of the molecular events during cartilage formation. However, a relatively few transcription factors have been proven to be involved in chondrogenesis.

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This study reports a new system that is very effective in identifying genes closely related to the early phase of chondrogenic differentiation. While studying chondrogenesis in a progenitor cell line, ATDC5, we found that the amount of culture media overlying an ATDC5 monolayer affected the extent to which differentiation occurred. Therefore, to gain insight into the molecular mechanisms of chondrogenic differentiation, differential gene expression between differentiating and non-differentiating ATDC5 cultures was examined by suppression subtractive hybridization analysis.

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Gene expression in human periodontal ligament (PDL) was examined by suppression subtractive hybridization to identify genes that are preferentially expressed in tissue compared to cultured PDL fibroblasts. The most enriched genes in a subtracted cDNA library are primarily genes for extracellular matrix components, types I and III collagen, lumican, periostin, and asporin, among others, whose expression conveys unique mechanical properties to the PDL. Also within this group is the gene for follicular dendritic cell secreted protein (FDC-SP), a small protein like statherin in saliva, not previously found in PDL.

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Mesenchymal cell condensation is an essential step for cartilage development. Versican/PG-M, a large chondroitin sulfate proteoglycan, is one of the major molecules expressed in the extracellular matrix during condensation. However, its role, especially as an environment for cells being condensed, has not been elucidated.

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We have developed a simple and unique strategy for identifying cell surface and extracellular matrix molecules produced by chondrocytes. Our strategy comprises two methods, retrovirus-based signal sequence gene trapping and culturing of Swarm rat chondrosarcoma chondrocytes. After infection with a retrovirus vector and isolation of hygromycin-resistant clones, trapped genes could be easily identified by the 5' rapid amplification of cDNA ends (5' RACE) method.

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