研究者詳細 - 沢　禎彦

論文 - 沢　禎彦

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Study of Podoplanin-Deficient Mouse Bone with Mechanical Stress. 査読国際誌

Takenori Kanai, Kyoko Osawa, Koichiro Kajiwara, Yoshiaki Sato, Yoshihiko Sawa

Dentistry journal 13 ( 2 ) 2025年1月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Objective: We investigated morphological differences in osteocyte processes between aged mice and our original podoplanin-conditional knockout (cKO) mice in which the floxed exon 3 of podoplanin was deleted by Dmp-1-driven Cre (Dmp1-Cre;PdpnΔ/Δ). Methods: SEM observation on osteocyte cell process, histochemistry for bone remodeling with mechanostress, and RT-PCR for RANKL and M-CSF in podoplanin cKO mouse bone with mechanostress was investigated. Results: SEM observations showed fewer and thinner osteocyte processes in femurs from 23-week-old Dmp1-Cre;PdpnΔ/Δ mice than from 23-week-old wild-type mice, while the numbers of osteocyte processes in femurs and calvarias were similar in 23-week-old Dmp1-Cre;PdpnΔ/Δ mice and 48-week-old wild-type mice. Furthermore, cell process numbers in femurs and calvarias were significantly smaller in 23-week-old Dmp1-Cre;PdpnΔ/Δ mice than in 48-week-old wild-type mice. In the test for differences in alveolar bone resorption under mechanical stress between Dmp1-Cre;PdpnΔ/Δ and wild-type mice, the area of TRAP-positive resorption pits was larger in wild-type mice than in Dmp1-Cre;PdpnΔ/Δ mice. In a quantitative tissue PCR analysis, the mRNA expression levels of RANKL and M-CSF in alveolar bone under mechanical stress were significantly lower in Dmp1-Cre;PdpnΔ/Δ mice than in wild-type mice. These results suggest that a reduction in cell process formation in osteocytes with podoplanin cKO affected the absorption of alveolar bone under mechanical stress in Dmp1-Cre;PdpnΔ/Δ mice. Conclusions: In podoplanin-deficient bone, the deformation of osteocyte processes by mechanical stimuli is not recognized as a stress due to the lower number of cell processes with podoplanin deficiency; therefore, the production of osteoclast migration/differentiation factors by activated osteocytes is not fully induced and macrophage migration to alveolar bone with mechanical stress appeared to be suppressed. These results indicate that podoplanin-dependent osteocyte process formation indirectly plays a key role in sensing mechanical stress in bone.

DOI： 10.3390/dj13020061

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Exacerbation of diabetes due to F. Nucleatum LPS-induced SGLT2 overexpression in the renal proximal tubular epithelial cells. 査読国際誌

Aiko Seki, Koichiro Kajiwara, Jumpei Teramachi, Masahiko Egusa, Takuya Miyawaki, Yoshihiko Sawa

BMC nephrology 26 ( 1 ) 38 - 38 2025年1月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Diabetes treatments by the control of sodium-glucose cotransporter 2 (SGLT2) is commonly conducted while there are still uncertainties about the mechanisms for the SGLT2 overexpression in kidneys with diabetes. Previously, we have reported that glomeruli and proximal tubules with diabetic nephropathy express toll-like receptor TLR2/4, and that the TLR ligand lipopolysaccharide (LPS) of periodontal pathogens have caused nephropathy in diabetic model mice. Recently, many researchers suggested that the periodontal pathogenic bacteria Fusobacterium (F.) nucleatum has the TLR4-associated strong activator of the colorectal inflammation and cancer. The present study aimed to investigate the possibility of F. nucleatum as an exacerbation factor of diabetes through the renal SGLT2 induction. METHODS: The induction of the SGLT2 by F. nucleatum LPS (Fn-LPS) were investigated in the streptozotocin-induced diabetic mouse renal tissue and cultured renal proximal epithelial cells. The changes of blood glucose levels and survival curves in diabetic mice with Fn-LPS were analyzed. The Fn-LPS-induced SGLT2 production in the diabetic mouse renal tissue and in the cultured proximal epithelial cells was examined by ELISA, quantitative RT-PCR, and immunohistochemical analysis. RESULTS: The SGLT2 expression in the cultured mouse tubular epithelial cells was significantly increased by TNF- or co-culture with Fn-LPS-supplemented J774.1 cells. The period to reach diabetic condition was significantly shorter in Fn-LPS-administered diabetic mice than in diabetic mice. All Fn-LPS-administered-diabetic mice reached humane endpoints during the healthy period of all of the mice administered Fn-LPS only. The promotion of the SGLT2 expression at the inner lumen of proximal tubules were stronger in the Fn-LPS-administered-diabetic mice than in diabetic mice. The renal tissue SGLT2 mRNA amounts and the number of renal proximal tubules with overexpressed SGLT2 in the lumen were more in the Fn-LPS-administered-diabetic mice than in diabetic mice. CONCLUSIONS: This study suggests that F. nucleatum causes the promotion of diabetes through the overexpression of SGLT2 in proximal tubules under the diabetic condition. Periodontitis with F. nucleatum may be a diabetic exacerbating factor.

DOI： 10.1186/s12882-025-03965-z

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The Abnormal Expression of Tubular SGLT2 and GULT2 in Diabetes Model Mice with Malocclusion-Induced Hyperglycemia. 査読国際誌

Koichiro Kajiwara, Sachio Tamaoki, Yoshihiko Sawa

Biomedicines 13 ( 2 ) 2025年1月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Background: A relationship between malocclusion and the promotion of diabetes has been suggested. In hyperglycemia, the expression of sodium-glucose cotransporter 2 (SGLT2) and the facilitative glucose transporter 2 (GLUT2) is upregulated in proximal tubular cells, leading to an increase in renal glucose reabsorption. The present study aimed to investigate whether malocclusion contributes to diabetic exacerbation. Methods: Streptozotocin (STZ)-induced diabetic mice with malocclusion due to cutting molars were investigated based on increased blood glucose levels. PCR and immunohistochemical analyses were performed on diabetic mice kidneys to investigate the expression of SGLT2 and GLUT2. Results: Animal experiments were performed using 32 mice for 21 days. The time to reach a diabetic condition in STZ-administered mice was shorter with malocclusion than without malocclusion. The increase and mean blood glucose levels in STZ-administered mice were steeper and higher with malocclusion than without malocclusion. Urea albumin, BUN, and CRE levels were higher in diabetic mice with malocclusion than in diabetic mice without. Immunoreaction with anti-SGLT2 and anti-GLUT2 in the renal tissue of STZ-administered mice was stronger with malocclusion than without malocclusion. The amounts of SGLT2 and GLUT2 mRNA in the renal tissue in STZ-administered mice were higher with malocclusion than without malocclusion. The amounts of TNF-a and IL-6 mRNA in the large intestinal tissue in STZ-administered mice were higher with malocclusion than without malocclusion. Conclusions: Our results indicate that malocclusion accelerates the tubular expression of SGLT2 and GLUT2 under hyperglycemia. Malocclusion may be a diabetes-exacerbating factor with increased poor glycemic control due to shortened occlusion time resulting from swallowing food without chewing.

DOI： 10.3390/biomedicines13020267

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ポドプラニンノックアウトマウスにおける下顎前歯歯槽骨の骨リモデリング機構について

梶原弘一郎, 沢禎彦, 玉置幸雄

日本矯正歯科学会大会プログラム・抄録集 83回 187 - 187 2024年10月

Morphological Study for the Osteocytes in Podoplanin-Conditional Knockout Mice 査読

Kyoko Osawa, Takenori Kanai, Natsumi Ushijima, Koichiro Kajiwara, Yoshihiko Sawa, Yoshiaki Sato

Journal of Hard Tissue Biology 32 ( 4 ) 213 - 222 2023年10月

糖尿病マウス腎におけるSGLT2 and VCAM-1発現について

梶原弘一郎, 沢禎彦

Journal of Oral Biosciences Supplement 2023 [P3 - 05 2023年9月

P.gingivalis LPS誘導性糖尿病モデルマウス腎でのSGLT2過剰発現について(Overexpression of SGLT2 in the kidney of a P.gingivalis LPS-induced diabetic nephropathy mouse model) 査読

梶原弘一郎, 沢禎彦

Journal of Oral Biosciences Supplement 2022 370 - 370 2022年9月

Maxillofacial morphological characteristics in growing orthodontic patients with non‐syndromic oligodontia 査読

Taiki Suyama, Hiroyuki Ishikawa, Sachio Tamaoki, Remi Higa, Shunsuke Takata, Yoshihiko Sawa

Orthodontics & Craniofacial Research 2021年12月

Overexpression of SGLT2 in the kidney of a P. gingivalis LPS-induced diabetic nephropathy mouse model. 査読国際誌

Koichiro Kajiwara, Yoshihiko Sawa

BMC Nephrology 22 ( 1 ) 287 - 287 2021年8月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The overexpression of sodium-glucose cotransporter 2 (SGLT2) in diabetic kidneys has been reported. It has also been established that the diabetic glomerular endothelium expresses the toll-like receptors TLR2 and TLR4. The present study aims to examine the renal SGLT2 induction by the TLR2/4 ligand Porphyromonas (P.) gingivalis lipopolysaccharide (Pg-LPS) in mouse diabetic nephropathy. METHODS: Immunohistochemical study and tissue RT-PCR analyses were performed on mouse kidneys in streptozotocin (STZ)-induced diabetic ICR mice (STZ-ICR), in healthy ICR mice administered Pg-LPS (LPS-ICR), and in diabetic ICR mouse kidneys with Pg-LPS-induced nephropathy (LPS-STZ). RESULTS: In the quantitative analysis of blood sugar levels, the mean time to reach 600 mg/dl was shorter in the LPS-STZ than in the STZ-ICR kidneys. The rise in blood glucose levels was significantly steeper in the LPS-STZ than in the STZ-ICR kidneys. According to these data the LPS-STZ model suggests a marked glucose intolerance. The expression of SGLT2 was significantly stronger in the whole of the renal parenchyma of the LPS-STZ than in the LPS-ICR or in the STZ-ICR. The expression of SGLT2 was observed both in the renal tubules and around the renal tubules, and in the glomeruli of the LPS-STZ kidneys. In the analysis by tissue real-time PCR and cell ELISA, the expression of the SGLT2 gene and protein was significantly stronger in the LPS-STZ than in the LPS-ICR or in the STZ-ICR. There were no differences in the renal SGLT2 production in the LPS-ICR and the STZ-ICR kidneys. CONCLUSIONS: Abnormally high renal expression of SGLT2 occurs in diabetic kidneys with P. gingivalis LPS. Periodontitis may be an exacerbating factor in diabetic nephropathy as well as in diabetes.

DOI： 10.1186/s12882-021-02506-8

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Expression of SARS-CoV-2 entry factors in human oral tissue. 査読国際誌

Yoshihiko Sawa, Soichiro Ibaragi, Tatsuo Okui, Junro Yamashita, Tetsuro Ikebe, Hiroyuki Harada

Journal of Anatomy 238 ( 6 ) 1341 - 1354 2021年6月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

The distribution of cells expressing SARS-CoV-2 entry factor angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in human oral tissues were tested. The investigation was conducted with normal flesh tissue and paraffin-embedded specimens. The ACE2 and TMPRSS2 expression was detected with all subjects in the normal mucosa of the keratinized stratified squamous epithelia of the tongue and non-keratinized stratified squamous epithelia of the lip and cheek. It was found that ACE2 is expressed in the cytoplasm and on the cell membrane mainly in the stratum granulosum of the epithelia while the TMPRSS2 is strongly expressed on the cell membrane mainly in the stratum granulosum and stratum spinosum, but not in the stratum basale. Antibodies' reactions for ACE2 and TMPRSS2 were not observed in the nuclei or keratin layer. The expression of ACE2 and TMPRSS2 in the oral epithelia appears to be general, and the expression was also observed in the mucous and serous acini of the labial glands. The SARS-CoV-2 may transiently attach to the oral mucosa and the minor salivary glands which are present under all of the oral mucosa. The oral cavity can be considered an important organ for SARS-CoV-2 attachment and may provide a preventive medical avenue to guard against COVID-19 by preventing saliva from scattering.

DOI： 10.1111/joa.13391

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Immunohistochemical study for the expression of leukocyte adhesion molecules, and FGF23 and ACE2 in P. gingivalis LPS-induced diabetic nephropathy. 査読国際誌

Koichiro Kajiwara, Yoshihiko Sawa, Takahiro Fujita, Sachio Tamaoki

BMC Nephrology 22 ( 1 ) 3 - 3 2021年1月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: The present study aims to examine the expression of leukocyte adhesion molecules and renal metabolic factors in diabetic mouse kidneys with periodontal pathogen Pg-LPS-induced nephropathy. BACKGROUND: We recently reported that the glomerular endothelium expresses toll-like receptor (TLR)2 and TLR4 in diabetic environments and TLR2/4 ligand Porphyromonas (P.) gingivalis lipopolysaccharides (Pg-LPS) induce nephropathy in diabetic mice. It is thought that Pg-LPS promotes the chronic inflammation with the overexpression of leukocyte adhesion molecules and renal-specific metabolic enzymes by the recognition of Pg-LPS via TLR in the diabetic kidneys. There have been no reports of the effects of periodontopathic bacteria on the expression of leukocyte adhesion molecules and the accumulation of physiologically active substances in the kidney. METHODS: The immunohistochemical investigation was performed on diabetic mouse kidney with Pg-LPS-induced nephropathy with glomerulosclerosis in glomeruli. RESULTS: There were no vessels which expressed vascular cell adhesion molecule-1 (VCAM-1), E-selectin, or fibroblast growth factor (FGF) 23 in streptozotocin (STZ)-induced diabetic ICR mice (STZ-ICR), or in healthy ICR mice administered Pg-LPS (LPS-ICR). However, in diabetic ICR mouse kidneys with Pg-LPS-induced nephropathy (LPS-STZ) the expression of VCAM-1 and the accumulation of FGF23 were observed in renal tubules and glomeruli, and the expression of E-selectin was observed in renal parenchyma and glomeruli. The angiotensin-converting enzyme 2 (ACE2) was detected in the proximal tubules but not in other regions of ICR, STZ-ICR, or LPS-ICR. In LPS-STZ ACE2 was detected both in renal tubules as well as in glomeruli. The Mac-1 and podoplanin-positive cells increased in the renal parenchyma with diabetic condition and there was the distribution of a large number of Mac-1-positive cells in LPS-STZ. CONCLUSIONS: The Pg-LPS may induce diabetic renal inflammation such as glomerulosclerosis and tubulitis with infiltration of Mac-1/podoplanin positive macrophages via glomerular overexpression of VCAM-1 and E-selectin, resulting in accumulation of both ACE2 and FGF23 which were unmetabolized with the inflammation-induced kidney damage under the diabetic condition. Periodontitis may be a critical factor in the progress of nephropathy in diabetic patients.

DOI： 10.1186/s12882-020-02203-y

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Cancellation of the Calcification in Cultured Osteoblasts by CLEC-2

Takenori Kanai, Yoshihiko Sawa, Yoshiaki Sato

Journal of Hard Tissue Biology 30 ( 1 ) 53 - 62 2021年

Effect of bisphosphonates on healing of tooth extraction wounds in infectious osteomyelitis of the jaw 査読国際誌

Junro Yamashita, Naruhiko Sawa, Yoshihiko Sawa, Shoji Miyazono

Bone 143 115611 - 115611 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier BV

OBJECTIVES: Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) and infectious osteomyelitis of the jaw (OMJ) in antiresorptive-naïve patients are different disease entities. Although osteoclast inhibition is at the center of the pathogenesis of ARONJ, the role of osteoclast inhibition in infectious OMJ is unknown. The objective of this study was to determine the effect of bisphosphonate osteoclast inhibition in infectious OMJ. METHODS: Osteomyelitis was induced in mice by S. aureus inoculation. The establishment of OMJ was verified by the culture of bone marrow samples obtained from the mandible. Infected animals received either zoledronic acid (ZA) or saline starting at week-2. Treated animals along with non-infected animals underwent tooth extractions at week-4 post-infection. Healing was assessed every week using in vivo micro-computed tomography and intraoral photos. Animals were euthanized at week-8 and cervical lymph nodes were assessed for lymphatic and blood vessels. RESULTS: Tooth extraction wounds did not heal in animals with OMJ. These wounds were characterized by incomplete soft tissue coverage, sporadic bone fill in the sockets, and inflammatory cell accumulation in the connective tissue at 4 weeks after tooth extractions. Conversely, the majority of tooth extraction wounds in the infected animals treated with ZA had improved healing with better bone fill than even non-infected control animals. Consistently, atrophic lymphatic vessels were noted in the draining lymph nodes in animals with OMJ. However, infected animals treated with ZA had lymphatic vessels that were unaltered and showed a similar appearance to those in non-infected control animals. CONCLUSION: ZA treatment promoted wound healing in the jaw with infectious osteomyelitis. Clearly, antiresorptive therapy is contraindicated in patients with ARONJ. However, our finding suggests that osteoclast inhibition is potentially an effectual remedy for infectious OMJ in antiresorptive-naïve patients.

DOI： 10.1016/j.bone.2020.115611

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Alternating Differentiation and Dedifferentiation between Mature Osteoblasts and Osteocytes. 国際誌

Naruhiko Sawa, Hiroki Fujimoto, Yoshihiko Sawa, Junro Yamashita

Scientific reports 9 ( 1 ) 13842 - 13842 2019年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Osteocytes are terminally differentiated osteoblasts embedded in the bone matrix. Evidence indicates that cells in the mesenchymal lineage possess plasticity. However, whether or not osteocytes have the capacity to dedifferentiate back into osteoblasts is unclear. This study aimed to clarify the dedifferentiation potential of osteocytes. Mouse calvarial osteoblasts were isolated and maintained in normal two-dimensional (2D) or collagen gel three-dimensional (3D) cultures. In 2D cultures, osteoblasts exhibited a typical fibroblast-like shape with high Alpl and minimal Sost, Fgf23, and Dmp1 expression and osteoblasts formed mineralised nodules. When these osteoblasts were transferred into 3D cultures, they showed a stellate shape with diminished cytoplasm and numerous long processes and expression of Alpl decreased while Sost, Fgf23, and Dmp1 were significantly increased. These cells were in cell cycle arrest and showed suppressed mineralisation, indicating that they were osteocytes. When these osteocytes were recovered from 3D cultures and cultured two-dimensionally again, they regained adequate cytoplasm and lost the long processes, resulting in a fibroblast-like shape. These cells showed high Alpl and low Sost, Fgf23, and Dmp1 expression with a high mineralisation capability, indicating that they were osteoblasts. This report shows that osteocytes possess the capacity to dedifferentiate back into mature osteoblasts without gene manipulation.

DOI： 10.1038/s41598-019-50236-7

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Alternating Differentiation and Dedifferentiation between Mature Osteoblasts and Osteocytes 査読国際誌

Sawa N, Fujimoto H, Sawa Y, Yamashita J

Scientific Reports 25;9 ( 1 ) 13842 - 21788 2019年9月

Maxillofacial morphological factors related to acceleration of maxillary growth attributed to facial mask treatment: a structural superimposition study. 査読国際誌

Takashi S Kajii, Yui Sakaguchi, Yoshihiko Sawa, Sachio Tamaoki

Progress in orthodontics 20 ( 1 ) 2 - 2 2019年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Anatomical textbooks mention that the contact between the pterygoid process and the palatine's pyramidal process is not a "suture" but "conjugation.".The aim was to evaluate the maxillofacial morphological factor responding most to the orthopedic force of facial mask treatment, using the structural superimposition analysis. METHODS: Thirty-one girls with Angle Class III malocclusion treated using a facial mask (FM group) and 11 girls with pseudo-Class III malocclusion (pseudo-III group) were examined. Lateral cephalograms at pre- and posttreatment were analyzed to evaluate maxillofacial changes. Cephalometric structural superimposition analysis originating with Björk and Skieller was also performed. RESULTS: In the FM group, a multiple linear regression model showed that maxillary sutural growth was significantly associated with counter-clockwise rotation of the maxilla and treatment changes in the anteroposterior distance from the pterygomaxillary fissure to the maxillary anterior alveolus, not changes in the distance from the nasion to the maxillary anterior alveolus. CONCLUSIONS: Structural superimposition analysis showed that counter-clockwise rotation of the maxilla and changes in the distance from the pterygomaxillary fissure to the maxillary anterior alveolus responded most to the orthopedic force of facial mask treatment. The analysis implicated that the pterygoid fissure-palatine's pyramidal process conjugation responds most to facial mask treatment among maxillofacial sutures and conjugation, and that the difference in the response induces maxillary counter-clockwise rotation.

DOI： 10.1186/s40510-018-0254-9

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LpMab-23-recognizing cancer-type podoplanin is a novel predictor for a poor prognosis of early stage tongue cancer 査読国際誌

Akihiro Miyazaki, Hiromi Nakai, Tomoko Sonoda, Yoshihiko Hirohashi, Mika K. Kaneko, Yukinari Kato, Yoshihiko Sawa, Hiroyoshi Hiratsuka

Oncotarget 9 ( 30 ) 21156 - 21165 2018年4月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Impact Journals LLC

Purpose: We report that the reactivity of a novel monoclonal antibody LpMab-23 for human cancer-type podoplanin (PDPN) is a predictor for a poor prognosis of tongue cancer. Patients and Methods: The association between LpMab-23-recognizing cancertype PDPN expression and clinical/pathological features were analyzed on 60 patients with stage I and II tongue cancer treated with transoral resection of the primary tumor. Results: In the mode of invasion, the LpMab-23-dull/negative cases were significantly larger in cases with low-grade malignancies and without late cervical lymph node metastasis, than in cases with high-grade malignancies and the metastasis. In the high-grade malignant cases, LpMab-23-positive cases were significantly larger than LpMab-23-dull/negative cases. The Kaplan-Meier curves of the five-year metastasis-free survival rate (MFS) were significantly lower in the LpMab-23 positive patients than in LpMab-23 dull/negative patients. The LpMab-23- dull/negative cases showed the highest MFS in all of the clinical/pathological features and particularly, the MFS of the LpMab-23 positive cases decreased to less than 60% in the first year. In the Cox proportional hazard regression models a comparison of the numbers of LpMab-23 dull/negative with positive cases showed the highest hazard ratio with statistical significance in all of the clinical/pathological features. Conclusions: LpMab-23 positive cases may be considered to present a useful predictor of poor prognosis for early stage tongue cancer.

DOI： 10.18632/oncotarget.24986

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Expression and dynamics of podoplanin in cultured osteoblasts with mechanostress and mineralization stimulus 査読

Tomohiro Takenawa, Takenori Kanai, Tetsuya Kitamura, Yoshitaka Yoshimura, Yoshihiko Sawa, Junichiro Iida

Acta Histochemica et Cytochemica 51 ( 1 ) 41 - 52 2018年

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Japan Society of Histochemistry and Cytochemistry

This study investigates the significance of the expression and dynamics of podoplanin in mechanostress and mineralization in cultured murine osteoblasts. Podoplanin increased in osteoblasts subjected to straining in non-mineralization medium, suggesting that the mechanostress alone is a podoplanin induction factor. In osteoblasts subjected to vertical elongation straining in the mineralization medium, the mRNA amounts of podoplanin, osteopontin, and osteocalcin were significantly larger than those in cells not subjected to straining, suggesting that mechanostress is the cause of a synergistic effect in the expression of these proteins. In osteoblasts in the mineralization medium, significant increases in osteocalcin mRNA occurred earlier in cells subjected to straining than in the cells not subjected to straining, suggesting that the mechanostress is a critical factor to enhance the expression of osteocalcin. Western blot and ELISA analysis showed increased podoplanin production in osteoblasts with longer durations of straining. There was significantly less mineralization product in osteoblasts with antibodies for podoplanin, osteopontin, and osteocalcin. There was also less osteopontin and osteocalcin produced in osteoblasts with anti-podoplanin. These findings suggest that mechanostress induces the production of podoplanin in osteoblasts and that podoplanin may play a role in mineralization in cooperation with bone-associated proteins.

DOI： 10.1267/ahc.17031

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The promotion of nephropathy by Porphyromonas gingivalis lipopolysaccharide via toll-like receptors 査読国際誌

Koichiro Kajiwara, Shunsuke Takata, Thao T. To, Kenyo Takara, Yuji Hatakeyama, Sachio Tamaoki, Richard Peters Darveau, Hiroyuki Ishikawa, Yoshihiko Sawa

Diabetology and Metabolic Syndrome 9 ( 1 ) 73 - 73 2017年9月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BioMed Central Ltd.

Background: Recently, we reported that toll-like receptor (TLR)2 and TLR4 localized on the glomerular endothelium in the glomeruli of streptozotocin (STZ)-induced type 1 diabetic mice and high fat diet feed-induced type 2 diabetic mice, and that periodontal pathogen Porphyromonas gingivalis LPS (Pg-LPS) administration lowered the survival rate of diabetic mice. The present study aims to examine the effect of TLR4 blocking on the suppression of Pg-LPS-induced diabetic nephropathy. Methods: The survival rate and morphological/biochemical features for streptozotocin-induced diabetic mice with Pg-LPS and TLR4 blocker eritoran administration were investigated by reporter gene assay, urine and blood analysis, immunohistochemistry, and real time-PCR. Results and Conclusions: All of the diabetic mice administered Pg-LPS were euthanized within the survival period of almost all of the diabetic mice. The blood urea nitrogen and creatinine, expression of TLR2 and TGF-b, and type 1 collagen accumulation, in the diabetic mice increased significantly with the Pg-LPS administration. In spite of the limited TLR4 activation with Pg-LPS, the TLR4 blocker eritoran decreased blood urea nitrogen and creatinine, and raised the survival rate of the Pg-LPS-administered diabetic mice slightly. The high expression levels of TLR2, TGF-b, and type 1 collagen in Pg-LPS-administered diabetic mice decreased with eritoran. Nuclear STAT3 which enhances TLR2 expression was detected in the TLR2-expressing glomeruli of diabetic mice. The TLR2 and STAT3 gene expression increased by the Pg-LPS administration but decreased with eritoran. These may suggest that Pg-LPS-induced diabetic nephropathy is mainly dependent on TLR2 signaling on glomerular endothelial cells, and that TLR4 blocker eritoran may play a role to slow the progress of diabetic nephropathy.

DOI： 10.1186/s13098-017-0271-8

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Distinct Role of Transforming Growth Factor-Beta 1 and Fibroblast Growth Factors in Human Amelobastoma Epithelial Cell Proliferation

Yuko Matsuda, Naoko Kamogashira, Yuji Hatakeyama, Toshinari Mikami, Kazuki Nakashima, Junko Hatakeyama, Sachio Tamaoki, Yoshihiko Sawa, Hiroyuki Ishikawa

Biochemistry and Molecular Biology 2 ( 1 ) 1 - 5 2017年9月

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