start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=2 article-no= start-page=61 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250129 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Study of Podoplanin-Deficient Mouse Bone with Mechanical Stress en-subtitle= kn-subtitle= en-abstract= kn-abstract=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;PdpnĢ/Ģ). 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;PdpnĢ/Ģ 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;PdpnĢ/Ģ 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;PdpnĢ/Ģ mice than in 48-week-old wild-type mice. In the test for differences in alveolar bone resorption under mechanical stress between Dmp1-Cre;PdpnĢ/Ģ and wild-type mice, the area of TRAP-positive resorption pits was larger in wild-type mice than in Dmp1-Cre;PdpnĢ/Ģ 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;PdpnĢ/Ģ 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;PdpnĢ/Ģ 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. en-copyright= kn-copyright= en-aut-name=KanaiTakenori en-aut-sei=Kanai en-aut-mei=Takenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OsawaKyoko en-aut-sei=Osawa en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KajiwaraKoichiro en-aut-sei=Kajiwara en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatoYoshiaki en-aut-sei=Sato en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SawaYoshihiko en-aut-sei=Sawa en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Orthodontics, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University kn-affil= affil-num=2 en-affil=Department of Orthodontics, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University kn-affil= affil-num=3 en-affil=Department of Oral Growth & Development, Hokkaido University kn-affil= affil-num=4 en-affil=Department of Orthodontics, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University kn-affil= affil-num=5 en-affil=Department of Oral Function & Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=podoplanin kn-keyword=podoplanin en-keyword=cKO kn-keyword=cKO en-keyword=osteocyte kn-keyword=osteocyte en-keyword=bone kn-keyword=bone en-keyword=remodeling kn-keyword=remodeling END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=2 article-no= start-page=267 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250122 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Abnormal Expression of Tubular SGLT2 and GULT2 in Diabetes Model Mice with Malocclusion-Induced Hyperglycemia en-subtitle= kn-subtitle= en-abstract= kn-abstract=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. en-copyright= kn-copyright= en-aut-name=KajiwaraKoichiro en-aut-sei=Kajiwara en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TamaokiSachio en-aut-sei=Tamaoki en-aut-mei=Sachio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SawaYoshihiko en-aut-sei=Sawa en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Oral Growth & Development, Fukuoka Dental College kn-affil= affil-num=2 en-affil=Department of Oral Growth & Development, Fukuoka Dental College kn-affil= affil-num=3 en-affil=Department of Oral Function & Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=malocclusion kn-keyword=malocclusion en-keyword= hyperglycemia kn-keyword= hyperglycemia en-keyword= SGLT2 kn-keyword= SGLT2 en-keyword= GLUT2 kn-keyword= GLUT2 END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=38 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250124 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exacerbation of diabetes due to F. Nucleatum LPS-induced SGLT2 overexpression in the renal proximal tubular epithelial cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=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. en-copyright= kn-copyright= en-aut-name=SekiAiko en-aut-sei=Seki en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KajiwaraKoichiro en-aut-sei=Kajiwara en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TeramachiJumpei en-aut-sei=Teramachi en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EgusaMasahiko en-aut-sei=Egusa en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyawakiTakuya en-aut-sei=Miyawaki en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SawaYoshihiko en-aut-sei=Sawa en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Oral Growth & Development, Fukuoka Dental College kn-affil= affil-num=3 en-affil=Department of Oral Function & Anatomy, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Dental Anesthesiology & Special Care Dentistry, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Dental Anesthesiology & Special Care Dentistry, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Oral Function & Anatomy, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=F. Nucleatum kn-keyword=F. Nucleatum en-keyword=Diabetic exacerbation kn-keyword=Diabetic exacerbation en-keyword=Diabetic nephropathy kn-keyword=Diabetic nephropathy en-keyword=SGLT2 kn-keyword=SGLT2 END start-ver=1.4 cd-journal=joma no-vol=238 cd-vols= no-issue=6 article-no= start-page=1341 end-page=1354 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202119 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Expression of SARS]CoV]2 entry factors in human oral tissue en-subtitle= kn-subtitle= en-abstract= kn-abstract=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f 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. en-copyright= kn-copyright= en-aut-name=SawaYoshihiko en-aut-sei=Sawa en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkuiTatsuo en-aut-sei=Okui en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamashitaJunro en-aut-sei=Yamashita en-aut-mei=Junro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkebeTetsuro en-aut-sei=Ikebe en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HaradaHiroyuki en-aut-sei=Harada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Oral Function & Anatomy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Center for Regenerative Medicine, Fukuoka Dental College kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Fukuoka Dental College kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Tokyo Medical and Dental University kn-affil= en-keyword=oral tissues kn-keyword=oral tissues en-keyword=SARS]CoV]2 kn-keyword=SARS]CoV]2 END