Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 26
Filter
Add more filters










Publication year range
1.
Cell Biol Int ; 47(10): 1737-1748, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37381608

ABSTRACT

Chondrogenesis is strictly regulated by several factors, including cytokines, hormones, and extracellular matrix proteins. Mouse teratocarcinoma-derived lineage cells, differentiate into chondrocytes in the presence of insulin. Although ascorbic acid promotes chondrogenic differentiation, the detailed regulative mechanisms underlying its role in chondrogenesis remain unclear. Therefore, in this study, we evaluated the effects of ascorbic acid on insulin-induced chondrogenic differentiation of ATDC5 cells and the underlying intracellular signaling. The results revealed that insulin-stimulated collagen deposition, matrix formation, calcification, and expression of chondrogenic differentiation marker genes in ATDC5 cells. This enhancement by insulin was amplified with the addition of ascorbic acid. Molecular analysis revealed that the activation of insulin-induced phosphoinositide 3-kinase (PI3K)/Akt signaling was enhanced in the presence of ascorbic acid. In contrast, Wnt/ß-catenin signaling was suppressed during chondrocyte differentiation via upregulation of the Wnt agonist, secreted Frizzled-related protein 1 (sFRP-1) and 3 (sFRP-3). Notably, ascorbic acid upregulated the expression of insulin receptors and their substrates (IRS-1 and IRS-2). Furthermore, ascorbic acid reversed the suppression of IRS-1 and IRS-2 protein by insulin. These results indicate that ascorbic acid positively regulates the chondrogenic differentiation of ATDC5 cells via enhancement of insulin signaling. Our findings provide a substantial basis for further elucidation of the regulatory mechanisms of chondrocyte differentiation and the pathophysiology of OA, thus aiding in development of effective treatment strategies.


Subject(s)
Ascorbic Acid , Chondrocytes , Animals , Mice , Ascorbic Acid/pharmacology , Chondrocytes/metabolism , Receptor, Insulin/metabolism , Chondrogenesis , Phosphatidylinositol 3-Kinases/metabolism , Cell Differentiation , Insulin/pharmacology , Insulin/metabolism , Wnt Signaling Pathway
2.
Oral Health Prev Dent ; 19(1): 405-409, 2021 Jan 07.
Article in English | MEDLINE | ID: mdl-34259433

ABSTRACT

PURPOSE: Tongue coating is one of the primary causes of halitosis and some diseases such as aspiration pneumonia. However, to date, an effective method for reducing the bacterial count of tongue coating has not been established. We conducted a randomised-controlled study to compare the efficacy of three types of disinfectants approved for oral use in Japan in reducing the bacterial count of tongue coating. MATERIALS AND METHODS: Thirty-two participants were randomly assigned to the following four groups according to the solution used: 1. benzethonium chloride; 2. povidone iodine; 3. hydrogen peroxide; 4. tap water (control group). Tongue cleaning with the three test disinfectants and water was performed using a toothbrush, and the bacterial count on the tongue dorsum before and after tongue cleaning was measured using the Rapid Oral Bacteria Quantification System. RESULTS: The bacterial count decreased statistically significantly after tongue brushing using povidone iodine and hydrogen peroxide solutions (both p = 0.012), but not after brushing using 0.2% benzethonium chloride and tap water. CONCLUSION: Tongue brushing with povidone iodine or hydrogen peroxide was the most effective method for reducing the bacterial count of tongue coating.


Subject(s)
Disinfectants , Halitosis , Bacterial Load , Halitosis/drug therapy , Halitosis/prevention & control , Humans , Japan , Tongue
3.
J Oral Sci ; 62(4): 449-451, 2020 Sep 26.
Article in English | MEDLINE | ID: mdl-32893198

ABSTRACT

The aim of the present study was to gather information to clarify the scope of oral health services in Asia, focusing particularly on the role of dental hygienists, anticipating that international exchange of data on oral health would benefit the establishment of such systems in other countries. Data on oral health providers were obtained from reliable sources, cited reports and professional websites, or from embassies of Asian countries located in Japan. The embassies were contacted by email, telephone, post, or interview. The survey was conducted from February 1, 2015, until June 18, 2019. Twenty-eight countries in Asia were selected according to their classification by the United Nations. Among them, 14 countries were found to recognize the professional status of dental hygienists. Nine of the 28 countries had no working dental hygienists, and their role was taken by other oral hygiene providers. It was unclear whether oral hygiene providers were operating in 5 of those countries. Many countries were found to lack formal oral health systems, and some had limited systems in rural areas. Dental hygienists work to prevent oral diseases in order to protect teeth and gums, as is the case in Japan. However, other oral health providers offer other dental services in other Asian countries, probably depending on individual national circumstances.


Subject(s)
Dental Hygienists , Oral Health , Asia , Humans , Japan , Scope of Practice
4.
Bone ; 132: 115209, 2020 03.
Article in English | MEDLINE | ID: mdl-31866495

ABSTRACT

Osteoclasts are multinuclear cells which maintain bone homeostasis by resorbing bone. During bone resorption, osteoclasts attach to the bone matrix via a sealing zone formed by an actin ring. Rous sarcoma oncogene (Src) is essential for actin ring formation and bone resorption. Recently, we demonstrated that plectin, a cytolinker protein, is a Src-binding protein in osteoclasts. However, the function of plectin in osteoclasts remains unknown. In this study, we demonstrated that shRNA knockdown of plectin in RAW 264.7 cells resulted in tartrate resistant acid phosphatase positive multinuclear cells (TRAP (+) MNCs) with impaired actin ring formation and bone resorption activity. Moreover, we found that in plectin-silenced TRAP (+) MNCs, Src and protein tyrosine kinase 2 beta (Pyk2), two critical kinases in osteoclastic bone resorption, were inactivated and microtubule polarity was disturbed. These results suggest that plectin plays a critical role in osteoclast biology by acting as a scaffold to facilitate Src and Pyk2 activation during microtubule organization.


Subject(s)
Bone Resorption , Focal Adhesion Kinase 2 , Cells, Cultured , Humans , Microtubules , Osteoclasts , Plectin/genetics
5.
Biochem Biophys Res Commun ; 512(3): 537-543, 2019 05 07.
Article in English | MEDLINE | ID: mdl-30914204

ABSTRACT

Hyaluronic acid (HA) has a pivotal role in bone and cartilage metabolism. In this study, we investigated the effect and underlying mechanisms of HA accumulation on the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) induced by 1α,25(OH)2D3 and dexamethasone in stromal cells, which support osteoclastogenesis. Degradation of HA by hyaluronidase (HA'ase) treatment enhanced the expression of RANKL in ST2 cells stimulated with 1α,25(OH)2D3 and dexamethasone. Down-regulation of hyaluronan synthase 2 (HAS2) expression by siRNA also stimulated RANKL expression induced by 1α,25(OH)2D3 and dexamethasone. Results from a cell co-culture system with bone marrow cell showed that 1α,25(OH)2D3 and dexamethasone-induced RANKL expression in HA'ase treated- and HAS2 siRNA transfected-ST2 cells was down-regulated by treatment of cells with high molecular weight HA. In contrast, transforming growth factor-ß1 (TGF-ß1), which stimulates HAS2 expression and HA synthesis, down-regulated RANKL expression induced by 1α,25(OH)2D3 and dexamethasone. Interestingly, knockdown of has2 gene enhanced the expression of vitamin D receptor (VDR) and phosphorylation of signal transducers and activator of transcription 3 (STAT3) in ST2 cells stimulated by 1α,25(OH)2D3 and dexamethasone. These results indicate that accumulation of HA in bone marrow cells may affect RANKL-mediated osteoclast-supporting activity via regulation of VDR and STAT3 signaling pathways.


Subject(s)
Hyaluronic Acid/metabolism , Osteogenesis , RANK Ligand/metabolism , Stromal Cells/metabolism , Animals , Cell Line , Cells, Cultured , Male , Mice , Osteoclasts/cytology , Osteoclasts/metabolism , Stromal Cells/cytology
6.
J Cell Biochem ; 120(8): 12604-12617, 2019 08.
Article in English | MEDLINE | ID: mdl-30825233

ABSTRACT

Macrophages, critical modulators of the immune response, polarize into various phenotypes, including M1 and M2. M1 macrophages are typically activated by lipopolysaccharide and produce proinflammatory cytokines. Conversely, M2 macrophages are activated by stimulation with interleukin 4 (IL)-4 and promote tissue remodeling and anti-inflammatory reactions. Recently, polyunsaturated fatty acids (PUFAs) have been shown to play important roles in the regulation of inflammation. Docosahexaenoic acid (DHA), a PUFA, has anti-inflammatory effects on chronic inflammatory disease, but its role in macrophage polarization remains unclear. In this study, we clarified the effects of DHA on macrophage polarization using U937 cells. Treatment with DHA resulted in upregulation of M2 macrophage markers and increased secretion of anti-inflammatory cytokines by U937 cells. IL-4, but not DHA, triggered phosphorylation of signal transducer and activator of transcription 6 (STAT6). DHA enhanced the expression of krüppel-like factor-4 (KLF4), a transcription factor involved in the regulation of macrophage polarization and increased the phosphorylation of p38 mitogen-activated protein kinase (MAPK). A selective inhibitor of p38 MAPK downregulated the expression of CD206 in DHA-treated U937 cells. Moreover, inhibitors of autophagy suppressed the phosphorylation of p38 MAPK and the expression of CD206 in DHA-treated U937 cells. Expression of microtubule-associated protein light chain 3-II, which is involved in autophagosome formation, was enhanced in DHA-treated U937 cells. Taken together, these results indicated that DHA enhanced the expression of M2 macrophage markers through the p38 MAPK signaling pathway and autophagy, suggesting that DHA regulates M2 macrophage polarization and plays an important role in innate immunity.


Subject(s)
Autophagy , Docosahexaenoic Acids/pharmacology , Inflammation , MAP Kinase Signaling System , Macrophages/drug effects , Anti-Inflammatory Agents/pharmacology , Docosahexaenoic Acids/metabolism , Humans , Interleukin-4/metabolism , Kruppel-Like Factor 4 , Macrophages/metabolism , Macrophages/physiology , THP-1 Cells , U937 Cells
7.
Oncotarget ; 10(3): 404-414, 2019 Jan 08.
Article in English | MEDLINE | ID: mdl-30719233

ABSTRACT

Melanoma, one of the most aggressive neoplasms, is characterized by rapid cell proliferation. Transducin-like Enhancer of Split (TLE) is an important regulator of cell proliferation via Histone deacetylase (HDAC) recruitment. Given that HDAC activity is associated with melanoma progression, we examined the relationship between TLE3, a TLE family member, and melanoma. TLE3 expression was increased during the progression of human patient melanoma (p < 0.05). Overexpression of Tle3 in B16 murine melanoma cells led to an increase in cell proliferation (p < 0.01) as well as the number of cyclinD1-positive cells. in vivo injection of mice with B16 cells overexpressing Tle3 resulted in larger tumor formation than in mice injected with control cells (p < 0.05). In contrast, siRNA-mediated knockdown of Tle3 in B16 cells or TLE3 in HMV-II human melanoma cells decreased proliferation (p < 0.01). Treatment of B16 cells with trichostatin A (2.5 µM), a class I and II HDAC inhibitor, prevented the effect s of Tle3 on proliferation. In conclusion, these data indicate that Tle3 is required, at least in part, for proliferation in the B16 mouse melanoma model.

8.
Arch Oral Biol ; 97: 185-190, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30391795

ABSTRACT

OBJECTIVE: It is important to protect the patient's oral mucosa from injury caused by inappropriate oral care. We established anin vivo model of intraepithelial injury of the oral mucosa and assessed the effects of inappropriate dental apparatus use on inflammatory response of macrophages in rats. DESIGN: Using this model, swabbing was performed to the labial mucosa of rats with the interdental brush, and the tissue samples were processed for histological evaluation. RESULTS: CD 68-positive macrophage-like cells appeared only in the subepithelial region after intraepithelial injury in the presence and absence of antibiotics. After intraepithelial injury, interleukin-1ß levels did not increase beyond those observed in intact rats. The number of bacteria in the lip increased slightly and decreased promptly. In the ear, intraepithelial injury caused an inflammatory response with macrophages infiltrating into the intraepithelial region as well as the subepithelial region, increased interleukin-1ß production, and high bacterial levels around tissues. CONCLUSION: Our results highlight the importance of protecting against the intraepithelial injury during oral care procedures, and these findings would contribute to oral care risk management in the future.


Subject(s)
Macrophages/physiology , Mouth Mucosa/cytology , Mouth Mucosa/injuries , Wound Healing/physiology , Animals , Enzyme-Linked Immunosorbent Assay , Interleukin-1beta/metabolism , Male , Rats , Rats, Wistar
9.
Cell Biol Int ; 42(12): 1622-1631, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30238554

ABSTRACT

Histone deacetylase has attracted much attention as an epigenetic factor, and the modulation of histone and transcription factor acetylation status is important for regulating gene expression. Moreover, histone deacetylase inhibitors are involved in cellular growth and differentiation. In the present study, we examined the effects of Ky-2, a hybrid-compound HDAC inhibitor, on inflammatory reactions and the polarization of macrophages in vitro. Human monocyte-like THP-1 cells were polarized to macrophage-like cells using phorbol 12-myristate 13-acetate, and then polarized to M1 macrophages with LPS. Ky-2 inhibited HDAC2 expression and enhanced the acetylation of histone H3 in THP-1 cells. It also downregulated the expression of the IL-1ß-encoding gene and the LPS-induced phosphorylation of p38 mitogen-activated protein kinases in THP-1 cells. Moreover, the expression of nod-like receptor protein 3 and cleaved caspase-1 p20 was downregulated in Ky-2-treated THP-1 cells. In contrast, this agent upregulated the expression of IL-1ra in LPS-treated THP-1 cells. These results indicate that Ky-2-treatment downregulates the expression of the inflammatory cytokine, IL-1ß, in LPS-treated THP-1 cells, suggesting that Ky-2 might regulate M1 macrophage polarization through the suppression of inflammatory responses such as NLRP3 inflammasome activation.


Subject(s)
Histone Deacetylase Inhibitors/pharmacology , Inflammation/pathology , Macrophages/pathology , Acetylation , Enzyme Activation/drug effects , Histone Deacetylase 2/metabolism , Histones/metabolism , Humans , Inflammasomes/metabolism , Interleukin 1 Receptor Antagonist Protein/metabolism , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Lipopolysaccharides , Mitogen-Activated Protein Kinases/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , THP-1 Cells
10.
Inflamm Regen ; 38: 16, 2018.
Article in English | MEDLINE | ID: mdl-29977413

ABSTRACT

BACKGROUND: Zoledronic acid (Zol), one of the bisphosphonates, is frequently utilized for the treatment of osteoporosis and bone metastasis. However, the onset of medication-related osteonecrosis of the jaw (MRONJ) following dental treatments has become a serious issue. We reported previously that osteonecrosis can be induced by Zol and lipopolysaccharide (LPS) in vivo, suggesting the involvement of Zol in inflammation. Macrophages are divided into M1/M2 macrophages. M1 macrophages are involved in the induction and exacerbation of inflammation and express proinflammatory mediators including interleukin (IL)-1. On the other hand, M2 macrophages are associated with anti-inflammatory reactions through the expression of anti-inflammatory cytokines, such as IL-10. In the present study, we clarified the effects of Zol on M1/M2 macrophage polarization in vitro. METHODS: Human monocytic THP-1 cells were polarized to macrophage-like cells by phorbol 12-myristate 13-acetate (PMA), and, after culturing for an additional 24 h with or without Zol, then polarized to M1 macrophages by LPS or to M2 macrophages by IL-4. Cell viability was examined by the WST-8 assay. Gene expression was confirmed by the real-time polymerase chain reaction. Protein expression was detected by western blotting and enzyme-linked immunosorbent assays. RESULTS: Zol treatment upregulated the expression of IL-1ß mRNA and protein through NLRP3 inflammasome activation in LPS-treated THP-1 cells. Zol treatment did not affect the expression of IL-10, IL-1ra, or CD206 in IL-4-treated THP-1 cells. CONCLUSIONS: Zol enhanced LPS-induced M1, but not M2, macrophage polarization through the NLRP3 inflammasome-dependent pathway, resulting in the production of inflammatory cytokines in THP-1 cells.

11.
Sci Rep ; 7(1): 16701, 2017 12 01.
Article in English | MEDLINE | ID: mdl-29196633

ABSTRACT

Glycerophospholipids have important structural and functional roles in cells and are the main components of cellular membranes. Glycerophospholipids are formed via the de novo pathway (Kennedy pathway) and are subsequently matured in the remodeling pathway (Lands' cycle). Lands' cycle consists of two steps: deacylation of phospholipids by phospholipases A2 and reacylation of lysophospholipids by lysophospholipid acyltransferases (LPLATs). LPLATs play key roles in the maturation and maintenance of the fatty acid composition of biomembranes, and cell differentiation. We examined whether LPLATs are involved in chondrogenic differentiation of ATDC5 cells, which can differentiate into chondrocytes. Lysophosphatidylcholine acyltransferase 4 (LPCAT4) mRNA expression and LPCAT enzymatic activity towards 18:1-, 18:2-, 20:4-, and 22:6-CoA increased in the late stage of chondrogenic differentiation, when mineralization occurred. LPCAT4 knockdown decreased mRNA and protein levels of chondrogenic markers as well as Alcian blue staining intensity and alkaline phosphatase activity in ATDC5 cells. These results suggest that LPCAT4 plays important roles during the transition of chondrocytes into hypertrophic chondrocytes and/or a mineralized phenotype.


Subject(s)
1-Acylglycerol-3-Phosphate O-Acyltransferase/metabolism , Chondrogenesis , 1-Acylglycerol-3-Phosphate O-Acyltransferase/antagonists & inhibitors , 1-Acylglycerol-3-Phosphate O-Acyltransferase/genetics , Animals , Bone Morphogenetic Protein 2/genetics , Bone Morphogenetic Protein 2/metabolism , Cell Differentiation , Cell Line , Core Binding Factor Alpha 1 Subunit/genetics , Core Binding Factor Alpha 1 Subunit/metabolism , Mice , RNA Interference , RNA, Small Interfering/metabolism
12.
FASEB J ; 30(7): 2591-601, 2016 07.
Article in English | MEDLINE | ID: mdl-27048541

ABSTRACT

Glycerophospholipids, which are components of biomembranes, are formed de novo by the Kennedy pathway and subsequently mature through the Lands cycle. Lysophospholipid acyltransferases (LPLATs) are key enzymes in both pathways and influence the fatty acid composition of biomembranes. Neuronal differentiation is characterized by neurite outgrowth, which requires biomembrane biosynthesis. However, the role of LPLATs in neuronal differentiation remains unknown. In this study, we examined whether LPLATs are involved in neuronal differentiation using all-trans-retinoic acid (ATRA)-treated P19C6 cells. In these cells, mRNA levels of lysophosphatidylethanolamine acyltransferase (LPEAT)-1/membrane-bound O-acyltransferase (MBOAT)-1 were higher than those in undifferentiated cells. LPEAT enzymatic activity increased with 16:0- and 18:1-CoA as acyl donors. When LPEAT1/MBOAT1 was knocked down with small interfering RNA (siRNA), outgrowth of neurites and expression of neuronal markers decreased in ATRA-treated P19C6 cells. Voltage-dependent calcium channel activity was also suppressed in these cells transfected with LPEAT1/MBOAT1 siRNA. These results suggest that LPEAT1/MBOAT1 plays an important role in neurite outgrowth and function.-Tabe, S., Hikiji, H., Ariyoshi, W., Hashidate-Yoshida, T., Shindou, H., Okinaga, T., Shimizu, T., Tominaga, K., Nishihara, T. Lysophosphatidylethanolamine acyltransferase 1/membrane-bound O-acyltransferase 1 regulates morphology and function of P19C6 cell-derived neurons.


Subject(s)
Acyltransferases/metabolism , Gene Expression Regulation, Enzymologic/physiology , Neurons/cytology , Acyltransferases/genetics , Animals , Cell Differentiation/physiology , Cell Line, Tumor , Gene Knockdown Techniques , Mice , Neurons/drug effects , Neurons/physiology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Tretinoin/pharmacology
13.
J Cell Biochem ; 116(12): 2840-8, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25994902

ABSTRACT

Lysophospholipid acyltransferases (LPLATs) regulate the diversification of fatty acid composition in biological membranes. Lysophosphatidylcholine acyltransferases (LPCATs) are members of the LPLATs that play a role in inflammatory responses. M1 macrophages differentiate in response to lipopolysaccharide (LPS) and are pro-inflammatory, whereas M2 macrophages, which differentiate in response to interleukin-4 (IL-4), are anti-inflammatory and involved in homeostasis and wound healing. In the present study, we showed that LPCATs play an important role in M1/M2-macrophage polarization. LPS changed the shape of PMA-treated U937 cells from rounded to spindle shaped and upregulated the mRNA and protein expression of the M1 macrophage markers CXCL10, TNF-α, and IL-1ß. IL-4 had no effect on the shape of PMA-treated U937 cells and upregulated the M2 macrophage markers CD206, IL-1ra, and TGF-ß in PMA-treated U937 cells. These results suggest that LPS and IL-4 promote the differentiation of PMA-treated U937 cells into M1- and M2-polarized macrophages, respectively. LPS significantly downregulated the mRNA expression of LPCAT3, one of four LPCAT isoforms, and suppressed its enzymatic activity toward linoleoyl-CoA and arachidonoyl-CoA in PMA-treated U937 cells. LPCAT3 knockdown induced a spindle-shaped morphology typical of M1-polarized macrophages, and increased the secretion of CXCL10 and decreased the levels of CD206 in IL-4-activated U937 cells. This indicates that knockdown of LPCAT3 shifts the differentiation of PMA-treated U937 cells to M1-polarized macrophages. Our findings suggest that LPCAT3 plays an important role in M1/M2-macrophage polarization, providing novel potential therapeutic targets for the regulation of immune and inflammatory disorders.


Subject(s)
1-Acylglycerophosphocholine O-Acyltransferase/metabolism , Cell Polarity/genetics , Inflammation/genetics , Macrophages/metabolism , 1-Acylglycerophosphocholine O-Acyltransferase/genetics , Cell Differentiation/drug effects , Cell Polarity/drug effects , Gene Expression Regulation, Developmental/drug effects , Humans , Inflammation/pathology , Interleukin-4/biosynthesis , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Phosphorylcholine/analogs & derivatives , Phosphorylcholine/pharmacology , Polymethacrylic Acids/pharmacology , RNA, Messenger/biosynthesis , U937 Cells
14.
J Mater Sci Mater Med ; 25(6): 1531-8, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24573457

ABSTRACT

Rapid and efficient animal models are needed for evaluating the effectiveness of many new candidate bone regenerative materials. We developed an in vivo model screening for calvarial bone regeneration in lipopolysaccharide (LPS)-treated mice, in which materials were overlaid on the periosteum of the calvaria in a 20 min surgery and results were detectable in 1 week. Intraperitoneal LPS injection reduced spontaneous bone formation, and local application of basic fibroblast growth factor (bFGF) increased the bone-forming activities of osteoblasts. A novel synthetic collagen gel, alkali-treated collagen (AlCol) cross-linked with trisuccinimidyl citrate (TSC), acted as a reservoir for basic substances such as bFGF. The AlCol-TSC gel in conjunction with bFGF activated osteoblast activity without the delay in osteoid maturation caused by bFGF administration alone. The AlCol-TSC gel may slow the release of bFGF to improve the imbalance between osteoid formation and bone mineralization. These findings suggest that our model is suitable for screening bone regenerative materials and that the AlCOl-TSC gel functions as a candidate reservoir for the slow release of bFGF.


Subject(s)
Bone Regeneration/physiology , Collagen/therapeutic use , Disease Models, Animal , Guided Tissue Regeneration/instrumentation , Skull Fractures/physiopathology , Skull Fractures/therapy , Tissue Scaffolds , Animals , Collagen/chemistry , Equipment Design , Gels/chemistry , Gels/therapeutic use , Humans , Materials Testing , Mice , Mice, Inbred BALB C , Skull , Skull Fractures/pathology , Treatment Outcome
15.
FASEB J ; 28(2): 871-9, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24221084

ABSTRACT

Although the roles of acids in bone metabolism are well characterized, the function of proton-sensing receptors in bone metabolism remains to be explored. In this study, we evaluated the role of proton-sensing receptor T-cell death-associated gene 8 (TDAG8) in osteoclastic activity during bone loss after ovariectomy. Through observations of bone mineral content, we found that pathological bone resorption was significantly exacerbated in mice homozygous for a gene trap mutation in the Tdag8 gene. Furthermore, osteoclasts from the homozygous mutant mice resorbed calcium in vitro more than the osteoclasts from the heterozygous mice did. Impaired osteoclast formation under acidic conditions was ameliorated in cultures of bone marrow cells by Tdag8 gene mutation. Extracellular acidification changed the cell morphology of osteoclasts via the TDAG8-Rho signaling pathway. These results suggest that the enhancement of TDAG8 function represents a new strategy for preventing bone resorption diseases, such as osteoporosis.


Subject(s)
Bone Resorption/metabolism , Osteoclasts/metabolism , Animals , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Female , Immunohistochemistry , In Situ Hybridization , Mice , Microscopy, Confocal , Ovariectomy , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Reverse Transcriptase Polymerase Chain Reaction
16.
J Bone Miner Res ; 28(12): 2449-62, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23526406

ABSTRACT

p130Cas, Crk-associated substrate (Cas), is an adaptor/scaffold protein that plays a central role in actin cytoskeletal reorganization. We previously reported that p130Cas is not tyrosine-phosphorylated in osteoclasts derived from Src-deficient mice, which are congenitally osteopetrotic, suggesting that p130Cas serves as a downstream molecule of c-Src and is involved in osteoclastic bone resorption. However, the physiological role of p130Cas in osteoclasts has not yet been confirmed because the p130Cas-deficient mice displayed embryonic lethality. Osteoclast-specific p130Cas conditional knockout (p130Cas(ΔOCL-) ) mice exhibit a high bone mass phenotype caused by defect in multinucleation and cytoskeleton organization causing bone resorption deficiency. Bone marrow cells from p130Cas(ΔOCL-) mice were able to differentiate into osteoclasts and wild-type cells in vitro. However, osteoclasts from p130Cas(ΔOCL-) mice failed to form actin rings and resorb pits on dentine slices. Although the initial events of osteoclast attachment, such as ß3-integrin or Src phosphorylation, were intact, the Rac1 activity that organizes the actin cytoskeleton was reduced, and its distribution was disrupted in p130Cas(ΔOCL-) osteoclasts. Dedicator of cytokinesis 5 (Dock5), a Rho family guanine nucleotide exchanger, failed to associate with Src or Pyk2 in osteoclasts in the absence of p130Cas. These results strongly indicate that p130Cas plays pivotal roles in osteoclastic bone resorption.


Subject(s)
Bone Resorption/metabolism , Bone Resorption/pathology , Crk-Associated Substrate Protein/metabolism , Osteoclasts/metabolism , Osteoclasts/pathology , Actins/metabolism , Animals , Bone and Bones/metabolism , Bone and Bones/pathology , Bone and Bones/ultrastructure , Cell Differentiation , Guanine Nucleotide Exchange Factors/metabolism , Integrins/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Models, Biological , Organ Size , Osteoblasts/metabolism , Osteoblasts/pathology , Osteoblasts/ultrastructure , Osteoclasts/ultrastructure , Osteogenesis , Phenotype , Signal Transduction , rac1 GTP-Binding Protein/metabolism
17.
J Dent Educ ; 75(4): 565-73, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21460278

ABSTRACT

The purpose of this article is to report changes to dental hygiene education in Japan and to evaluate the successful implementation of these changes in 2010. The legislative change that began in 2005 revised the length of education for dental hygiene students from two years to three or four years (the mandate was three years), which has led to a dramatic change in program curriculum. After a five-year moratorium, a new curriculum has been established for dental hygiene education in Japan. The new curriculum provides students the requisite knowledge to effectively perform the latest dental hygiene procedures. Although the change of the educational system from the present mandatory three-year to the new four-year programs poses many administrative problems, we believe this shift will ultimately provide a more thorough and in-depth education for students.


Subject(s)
Curriculum , Dental Hygienists/education , Education, Professional/organization & administration , Education, Professional/trends , Education, Professional/standards , Humans , Japan , Licensure , Specialties, Dental/education , Time Factors
18.
Article in English | MEDLINE | ID: mdl-20367061

ABSTRACT

There are various techniques for palatoplasty, but no studies of postoperative osteogenesis at the palatal fissure. In the cranial and maxillofacial region it is thought to develop from the periosteum, so palatoplasty with mucoperiosteal flaps may encourage new bone to form at the fissure. We evaluated the status of osteogenesis in the hard palate after palatoplasty on computed tomograms (CT). We studied 29 patients (22 boys and 7 girls) with unilateral cleft lip and palate who had pushback palatoplasty with the use of CT obtained between May 2003 and March 2007. Age at the time of operation was recorded. The width of the palatal fissure at the first premolar, the first molar, and the maxillary posterior region were measured on coronal CT. The mean (SD) age at the time of palatoplasty was 16 (2) months. The mean (SD) width of the fissure at the first molar was 3.96 (3.1) mm, and bony union was seen in four patients. The width of the fissure was significantly less at the first molar than at the other sites (p = 0.006). The shape of the margin of the fissure was irregular in nearly all patients. The width of the fissure at the first molar became significantly less, suggesting that osteogenesis had occurred. In some patients the height of the fissure differed. Given the results of previous studies, bony regeneration from the periosteum most likely happens together with regeneration from the margins of the fissure.


Subject(s)
Cleft Lip/surgery , Cleft Palate/surgery , Osteogenesis , Palate, Hard/diagnostic imaging , Female , Humans , Imaging, Three-Dimensional , Infant , Male , Palate, Hard/growth & development , Tomography, X-Ray Computed
19.
Proc Natl Acad Sci U S A ; 106(50): 21294-9, 2009 Dec 15.
Article in English | MEDLINE | ID: mdl-19965376

ABSTRACT

Although leukotriene B(4) (LTB(4)) is produced in various inflammatory diseases, its functions in bone metabolism remain unknown. Using mice deficient in the high-affinity LTB(4) receptor BLT1, we evaluated the roles of BLT1 in the development of two bone resorption models, namely bone loss induced by ovariectomy and lipopolysaccharide. Through observations of bone mineral contents and bone morphometric parameters, we found that bone resorption in both models was significantly attenuated in BLT1-deficient mice. Furthermore, osteoclasts from BLT1-deficient mice showed reduced calcium resorption activities compared with wild-type osteoclasts. Osteoclasts expressed BLT1, but not the low-affinity LTB(4) receptor BLT2, and produced LTB(4). LTB(4) changed the cell morphology of osteoclasts through the BLT1-Gi protein-Rac1 signaling pathway. Given the causal relationship between osteoclast morphology and osteoclastic activity, these findings suggest that autocrine/paracrine LTB(4) increases the osteoclastic activity through the BLT1-Gi protein-Rac1 signaling pathway. Inhibition of BLT1 functions may represent a strategy for preventing bone resorption diseases.


Subject(s)
Bone Resorption/etiology , Receptors, Leukotriene B4/physiology , Animals , Calcium/metabolism , Cell Communication , Cell Shape/drug effects , Leukotriene B4/pharmacology , Mice , Mice, Knockout , Osteoclasts/metabolism , Receptors, Leukotriene B4/deficiency , Signal Transduction
20.
Prog Lipid Res ; 47(2): 107-26, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18187046

ABSTRACT

The production of a variety of lipid mediators is enhanced in bone-resorptive diseases such as osteoporosis, rheumatoid arthritis, osteoarthritis, and periodontitis. Prostaglandin E(2) (PGE(2)) is one of the most notable lipid mediators of bone remodeling, and has been linked clinically to many bone-resorptive diseases. In vitro studies with bone cell cultures have demonstrated that the bone-resorptive activity of PGE(2), which is mediated by receptor activator of NF-kappaB ligand (RANKL), is key for the induction of osteoclast formation. Furthermore, interleukin (IL)-1- and IL-6-stimulated bone resorption involves PGE(2) production. In addition to its bone-resorptive effects, PGE(2) promotes bone formation in vitro by stimulating osteoblastic proliferation and differentiation. The multifaceted nature of PGE(2) makes it difficult to discern its role during bone remodeling. Leukotrienes (LTs), and particularly LTB(4), have also been implicated in bone remodeling and disease-specifically in rheumatoid arthritis. Moreover, recent studies from our laboratory have shown that platelet-activating factor (PAF) receptor-deficient mice develop only mild osteoporosis. Osteoclast survival in these mice is shortened and osteoclastic bone resorption is impaired. This review article focuses on these families of lipids and their function during bone metabolism and disease.


Subject(s)
Bone Diseases/metabolism , Bone and Bones/metabolism , Leukotrienes/physiology , Platelet Activating Factor/physiology , Prostaglandins/physiology , Animals , Arthritis, Rheumatoid/metabolism , Cell Differentiation , Dogs , Extracellular Matrix/metabolism , Fractures, Bone/metabolism , Humans , Interleukins/metabolism , Mice , Osteoblasts/metabolism , Peptide Hydrolases/metabolism , Periodontitis/metabolism , Prostaglandins/metabolism , RANK Ligand/metabolism , Rats , Receptors, Prostaglandin E/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...