Ovid Technologies (Wolters Kluwer Health)Acta Medica Okayama2169-75741422026A Technique for Repositioning the Posteriorly Displaced Premaxilla Following Prior Repair of Complete Bilateral Cleft Lipe7467ENYukiArimuraDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeijiIidaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAikoHyodoAdvanced Cleft Lip and Cleft Palate Center, Okayama University HospitalAyakaMikamiDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoruHayanoAdvanced Cleft Lip and Cleft Palate Center, Okayama University HospitalFumikoTakemotoAdvanced Cleft Lip and Cleft Palate Center, Okayama University HospitalHiroshiKamiokaAdvanced Cleft Lip and Cleft Palate Center, Okayama University HospitalIt is well known that osteotomy of the premaxilla is an effective surgical procedure for the correction of a displaced premaxilla in patients with bilateral cleft lip and palate. In cases with a posteriorly displaced premaxilla, it is not easy to move the premaxilla forward because of scarring of the palatal mucosal attachment, narrowing of the adjacent maxillary segments, and the stable fixation of this bone segment after its movement. This fixation is also important in cases without secondary bone grafting. We propose a new method that combines osteotomy and a method such as bone distraction for cases with significant premaxilla displacement that are difficult to repair by osteotomy alone. A conventional orthodontic palatal expander was used as the distractor. The anterior arms were bent at the posterior part of the lingual side of the anterior teeth, and a resin base was attached to the arm parts. The posterior arms were bent and waxed onto the bands of both first molars. Supportive stainless steel wire arms, which are attached to the rest of the deciduous molars, stabilize the distractor. After the osteotomy of the premaxilla, distraction was performed at a rate of 1.0 mm per day, starting the day after surgery. Because the premaxilla of patients with bilateral cleft lip and palate has undergone multiple surgical interventions, the soft tissue is not mobile, making it impossible to guide the premaxilla to an ideal position in a single stage. However, this procedure, using this semirigid distractor, makes it possible to move the osteotomized premaxilla to the planned position with firm stability.No potential conflict of interest relevant to this article was reported.BMCActa Medica Okayama1472-68312412024Histological differences related to autophagy in the minor salivary gland between primary and secondary types of Sjögren's syndrome1099ENHitomiOno-MinagiDepartment of Cytology and Histology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTsutomuNohnoDepartment of Cytology and Histology, Okayama University Medical SchoolKiyofumiTakabatakeDepartment of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakehiroTanakaDepartment of Pathology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakayukiKatsuyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University HospitalKohtaMiyawakiDivision of Precision Medicine, Kyushu University School of MedicineJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySoichiroIbaragiDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySeijiIidaDepartment of Oral and Maxillofacial Reconstructive Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTadashiYoshinoDepartment of Pathology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHitoshiNagatsukaDepartment of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakayoshiSakaiDepartment of Rehabilitation for Orofacial Disorders, Osaka University Graduate School of DentistryHideyoOhuchiDepartment of Cytology and Histology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySome forms of Sjögren’s syndrome (SS) follow a clinical course accompanied by systemic symptoms caused by lymphocyte infiltration and proliferation in the liver, kidneys, and other organs. To better understand the clinical outcomes of SS, here we used minor salivary gland tissues from patients and examine their molecular, biological, and pathological characteristics. A retrospective study was performed, combining clinical data and formalin-fixed paraffin-embedded (FFPE) samples from female patients over 60 years of age who underwent biopsies at Okayama University Hospital. We employed direct digital RNA counting with nCounter® and multiplex immunofluorescence analysis with a PhenoCycler™ on the labial gland biopsies. We compared FFPE samples from SS patients who presented with other connective tissue diseases (secondary SS) with those from stable SS patients with symptoms restricted to the exocrine glands (primary SS). Secondary SS tissues showed enhanced epithelial damage and lymphocytic infiltration accompanied by elevated expression of autophagy marker genes in the immune cells of the labial glands. The close intercellular distance between helper T cells and B cells positive for autophagy-associated molecules suggests accelerated autophagy in these lymphocytes and potential B cell activation by helper T cells. These findings indicate that examination of FFPE samples from labial gland biopsies can be an effective tool for evaluating molecular histological differences between secondary and primary SS through multiplexed analysis of gene expression and tissue imaging.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0031-6768476112024The role of GABA in modulation of taste signaling within the taste bud17611775ENAyakaMikamiDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHaiHuangDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAikoHyodoDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKengoHorieDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeikoYasumatsuTokyo Dental Junior CollegeYuzoNinomiyaDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshihiroMitohDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySeijiIidaDepartment of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyusukeYoshidaDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTaste buds contain 2 types of GABA-producing cells: sour-responsive Type III cells and glial-like Type I cells. The physiological role of GABA, released by Type III cells is not fully understood. Here, we investigated the role of GABA released from Type III cells using transgenic mice lacking the expression of GAD67 in taste bud cells (Gad67-cKO mice). Immunohistochemical experiments confirmed the absence of GAD67 in Type III cells of Gad67-cKO mice. Furthermore, no difference was observed in the expression and localization of cell type markers, ectonucleoside triphosphate diphosphohydrolase 2 (ENTPD2), gustducin, and carbonic anhydrase 4 (CA4) in taste buds between wild-type (WT) and Gad67-cKO mice. Short-term lick tests demonstrated that both WT and Gad67-cKO mice exhibited normal licking behaviors to each of the five basic tastants. Gustatory nerve recordings from the chorda tympani nerve demonstrated that both WT and Gad67-cKO mice similarly responded to five basic tastants when they were applied individually. However, gustatory nerve responses to sweet–sour mixtures were significantly smaller than the sum of responses to each tastant in WT mice but not in Gad67-cKO mice. In summary, elimination of GABA signalling by sour-responsive Type III taste cells eliminates the inhibitory cell–cell interactions seen with application of sour–sweet mixtures.No potential conflict of interest relevant to this article was reported.American Society for Clinical InvestigationActa Medica Okayama2379-37089102024Double-faced CX3CL1 enhances lymphangiogenesis-dependent metastasis in an aggressive subclone of oral squamous cell carcinomae174618ENHtoo ShweEainDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHotakaKawaiDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasaakiNakayamaDepartment of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMay WathoneOoDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiakiOharaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitYokoFukuharaDepartment of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKiyofumiTakabatakeDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityQuishengShanDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYaminSoeDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKishoOnoDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeisukeNakanoDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNobuyoshiMizukawaDepartment of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySeijiIidaDepartment of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHitoshiNagatsukaDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBecause cancer cells have a genetically unstable nature, they give rise to genetically different variant subclones inside a single tumor. Understanding cancer heterogeneity and subclone characteristics is crucial for developing more efficacious therapies. Oral squamous cell carcinoma (OSCC) is characterized by high heterogeneity and plasticity. On the other hand, CX3C motif ligand 1 (CX3CL1) is a double-faced chemokine with anti- and pro -tumor functions. Our study reported that CX3CL1 functioned differently in tumors with different cancer phenotypes, both in vivo and in vitro. Mouse OSCC 1 (MOC1) and MOC2 cells responded similarly to CX3CL1 in vitro. However, in vivo, CX3CL1 increased keratinization in indolent MOC1 cancer, while CX3CL1 promoted cervical lymphatic metastasis in aggressive MOC2 cancer. These outcomes were due to double-faced CX3CL1 effects on different immune microenvironments indolent and aggressive cancer created. Furthermore, we established that CX3CL1 promoted cancer metastasis via the lymphatic pathway by stimulating lymphangiogenesis and transendothelial migration of lymph -circulating tumor cells. CX3CL1 enrichment in lymphatic metastasis tissues was observed in aggressive murine and human cell lines. OSCC patient samples with CX3CL1 enrichment exhibited a strong correlation with lower overall survival rates and higher recurrence and distant metastasis rates. In conclusion, CX3CL1 is a pivotal factor that stimulates the metastasis of aggressive cancer subclones within the heterogeneous tumors to metastasize, and our study demonstrates the prognostic value of CX3CL1 enrichment in long-term monitoring in OSCC.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0003-99691652024Salivary buffering capacity is correlated with umami but not sour taste sensitivity in healthy adult Japanese subjects106013ENAikoHyodoDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAyakaMikamiDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKengoHorieDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshihiroMitohDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYuzoNinomiyaDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySeijiIidaDepartment of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyusukeYoshidaDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityObjective: Saliva serves multiple important functions crucial for maintaining a healthy oral and systemic environment. Among them, the pH buffering effect, which is primarily mediated by bicarbonate ions, helps maintain oral homeostasis by neutralizing acidity from ingested foods. Therefore, higher buffering capacity, reflecting the ability to neutralize oral acidity, may influence taste sensitivity, especially for sour taste since it involves sensing H+ ions. This study aims to explore the relationship between salivary buffering capacity and taste sensitivities to the five basic tastes in healthy adult humans.<br>
Design: Eighty seven healthy adult students participated in this study. Resting saliva volume was measured using the spitting method. The liquid colorimetric test was used to assess salivary buffering capacity. The whole-mouth taste testing method was employed to determine the recognition threshold for each tastant (NaCl, sucrose, citric acid, quinine-HCl, monosodium glutamate).<br>
Results: Taste recognition thresholds for sour taste as well as sweet, salty, and bitter tastes showed no correlation with salivary buffering capacity. Interestingly, a negative relationship was observed between recognition threshold for umami taste and salivary buffering capacity. Furthermore, a positive correlation between salivary buffering capacity and resting saliva volume was observed.<br>
Conclusions: Salivary buffering capacity primarily influences sensitivity to umami taste, but not sour and other tastes.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1873-96011742023Expression and function of CCN2-derived circRNAs in chondrocytes15011515ENSomaKatoDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazumiKawataDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiNishidaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomomiMizukawaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasaharuTakigawaAdvanced Research Center for Oral and Craniofacial Sciences, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesSeijiIidaDepartment of Oral Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiKubotaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCellular communication network factor 2 (CCN2) molecules promote endochondral ossification and articular cartilage regeneration, and circular RNAs (circRNAs), which arise from various genes and regulate gene expression by adsorbing miRNAs, are known to be synthesized from CCN2 in human vascular endothelial cells and other types of cells. However, in chondrocytes, not only the function but also the presence of CCN2-derived circRNA remains completely unknown. In the present study, we investigated the expression and function of CCN2-derived circRNAs in chondrocytes. Amplicons smaller than those from known CCN2-derived circRNAs were observed using RT-PCR analysis that could specifically amplify CCN2-derived circRNAs in human chondrocytic HCS-2/8 cells. The nucleotide sequences of the PCR products indicated novel circRNAs in the HCS-2/8 cells that were different from known CCN2-derived circRNAs. Moreover, the expression of several Ccn2-derived circRNAs in murine chondroblastic ATDC5 cells was confirmed and observed to change alongside chondrocytic differentiation. Next, one of these circRNAs was knocked down in HCS-2/8 cells to investigate the function of the human CCN2-derived circRNA. As a result, CCN2-derived circRNA knockdown significantly reduced the expression of aggrecan mRNA and proteoglycan synthesis. Our data suggest that CCN2-derived circRNAs are expressed in chondrocytes and play a role in chondrogenic differentiation.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7712023Osteonecrosis of the Jaw in Two Rheumatoid Arthritis Patients Not Treated with a Bisphosphonate111116ENKatsuhikoAmanoDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkinariSugauchiThe first department of Oral and Maxillofacial Surgery, Osaka University Graduate School of DentistryChiakiYamadaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikihikoKogoThe first department of Oral and Maxillofacial Surgery, Osaka University Graduate School of DentistrySeijiIidaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/64371Medication-related osteonecrosis of the jaw (MRONJ) is a side effect in patients taking bone-modifying agents (BMAs), which are highly beneficial for treating osteoporosis and cancer. Bisphosphonates are prescribed to treat secondary osteoporosis in patients with rheumatoid arthritis (RA). We recently encountered two unusual cases of intraoral ONJ in RA patients who had not been treated with a BMA and did not have features of methotrexate- associated lymphoproliferative disorder. Their ONJ stage II bone exposures were treated by conservative therapy, providing good prognoses. These cases indicate that ONJ can occur in RA patients not treated with bisphosphonates. Several risk factors are discussed.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7712023Treatment of Severe Open Bite Malocclusion with Four-Piece Segmental Horseshoe Le Fort I Osteotomy97104ENMitsuhiroHoshijimaDepartment of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaokiOkaDepartment of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTatsushiMatsumuraDepartment of Oral and Maxillofacial Surgery, Wakayama Medical UniversitySeijiIidaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiKamiokaDepartment of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/64369Appropriate operations in severe anterior open bite (AOB) cases are extremely complicated to perform because of the multiple surgical procedures involved, the difficulty of predicting posttreatment aesthetics, and the high relapse rate. We herein report a 16-year-old girl with skeletal Class II, severe AOB malocclusion, and crowding with short roots, and aesthetic and functional problems. Four-piece segmental Le Fort I osteotomy with horseshoe osteotomy was performed for maxillary intrusion, and bilateral sagittal split ramus osteotomy (SSRO) and genioplasty were performed for mandibular advancement. The malocclusion and skeletal deformity were significantly improved by the surgical orthodontic treatment. Functional and aesthetic occlusion with an improved facial profile was established, and no further root shortening was observed. Acceptable occlusion and dentition were maintained after a two-year retention period. This strategy of surgical orthodontic treatment with a complicated operative procedure might be effective for correcting certain severe AOB malocclusion cases.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1422-006722222021Comparing the Osteogenic Potential and Bone Regeneration Capacities of Dedifferentiated Fat Cells and Adipose-Derived Stem Cells In Vitro and In Vivo: Application of DFAT Cells Isolated by a Mesh Method12392ENKiyofumiTakabatakeDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasakazuMatsubaraDepartment of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityEikiYamachikaDepartment of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiFujitaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University HospitalYukiArimuraDepartment of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazukiNakatsujiDepartment of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeisukeNakanoDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHistoshiNagatsukaDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeijiIidaDepartment of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground: We investigated and compared the osteogenic potential and bone regeneration capacities of dedifferentiated fat cells (DFAT cells) and adipose-derived stem cells (ASCs). <br>
Method: We isolated DFAT cells and ASCs from GFP mice. DFAT cells were established by a new culture method using a mesh culture instead of a ceiling culture. The isolated DFAT cells and ASCs were incubated in osteogenic medium, then alizarin red staining, alkaline phosphatase (ALP) assays, and RT-PCR (for RUNX2, osteopontin, DLX5, osterix, and osteocalcin) were performed to evaluate the osteoblastic differentiation ability of both cell types in vitro. In vivo, the DFAT cells and ASCs were incubated in osteogenic medium for four weeks and seeded on collagen composite scaffolds, then implanted subcutaneously into the backs of mice. We then performed hematoxylin and eosin staining and immunostaining for GFP and osteocalcin. <br>
Results: The alizarin red-stained areas in DFAT cells showed weak calcification ability at two weeks, but high calcification ability at three weeks, similar to ASCs. The ALP levels of ASCs increased earlier than in DFAT cells and showed a significant difference (p < 0.05) at 6 and 9 days. The ALP levels of DFATs were higher than those of ASCs after 12 days. The expression levels of osteoblast marker genes (osterix and osteocalcin) of DFAT cells and ASCs were higher after osteogenic differentiation culture. <br>
Conclusion: DFAT cells are easily isolated from a small amount of adipose tissue and are readily expanded with high purity; thus, DFAT cells are applicable to many tissue-engineering strategies and cell-based therapies.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7522021Camouflage Treatment for Skeletal Maxillary Protrusion and Lateral Deviation with Classic-Type Ehlers-Danlos Syndrome205212ENMitsuhiroHoshijimaDepartment of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNoriakiKawanabeDepartment of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeijiIidaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiYamashiroDepartment of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, Osaka UniversityHiroshiKamiokaDepartment of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/61902We herein report the case of a 19-year-old female with a transverse discrepancy, skeletal Class II malocclusion, severe crowding with concerns of classic-type Ehlers-Danlos syndrome (EDS), aesthetics problems and functional problems. The main characteristics of classic EDS are loose-jointedness and fragile, easily bruised skin that heals with peculiar “cigarette-paper” scars. The anteroposterior and transverse skeletal discrepancies can generally be resolved by maxilla repositioning and mandibular advancement surgery following pre-surgical orthodontic treatment. However, this patient was treated with orthodontic camouflage but not orthognathic surgery because of the risks of skin bruising, poor healing and a temporomandibular disorder. A satisfactory dental appearance and occlusion were achieved after camouflage treatment with orthodontic anchor screws and the use of Class II elastics, including the preservation of the stomatognathic functions. Acceptable occlusion and dentition were maintained after a two-year retention period. This treatment strategy of orthodontic camouflage using temporary anchorage, such as anchor screws and Class II elastics, may be a viable treatment option for skeletal malocclusion patients with EDS.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama134900796232020Regulation of cellular communication network factor 2 (CCN2) in breast cancer cells via the cell-type dependent interplay between CCN2 and glycolysis280288ENShoAkashi Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiNishidaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomomiMizukawaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazumiKawataDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasaharuTakigawaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeijiIida Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiKubotaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesObjectives: Anti-osteoclastic treatments for breast cancer occasionally cause medication-related osteonecrosis of the jaw. Moreover, elevated glycolytic activity, which is known as the Warburg effect, is usually observed in these breast cancer cells. Previously, we found that cellular communication network factor 2 (CCN2) production and glycolysis enhanced each other in chondrocytes. Here, we evaluated the interplay between CCN2 and glycolysis in breast cancer cells, as we suspected a possible involvement of CCN2 in the Warburg effect in highly invasive breast cancer cells. <br/>
Methods: Two human breast cancer cell lines with a distinct phenotype were used. Glycolysis was inhibited by using 2 distinct compounds, and gene silencing was performed using siRNA. Glycolysis and the expression of relevant genes were monitored via colorimetric assays and quantitative RT-PCR, respectively. <br/>
Results: Although CCN2 expression was almost completely silenced when treating invasive breast cancer cells with a siRNA cocktail against CCN2, glycolytic activity was not affected. Notably, the expression of glycolytic enzyme genes, which was repressed by CCN2 deficiency in chondrocytes, tended to increase upon CCN2 silencing in breast cancer cells. Inhibition of glycolysis, which resulted in the repression of CCN2 expression in chondrocytic cells, did not alter or strongly enhanced CCN2 expression in the invasive and non-invasive breast cancer cells, respectively. <br/>
Conclusions: High CCN2 expression levels play a critical role in the invasion and metastasis of breast cancer. Thus, a collapse in the intrinsic repressive machinery of CCN2 due to glycolysis may induce the acquisition of an invasive phenotype in breast cancer cells. No potential conflict of interest relevant to this article was reported.Nature Publishing GroupActa Medica Okayama2045-232292019Intermittent parathyroid hormone 1-34 induces oxidation and deterioration of mineral and collagen quality in newly formed mandibular bone8041ENYohsukeYoshiokaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEikiYamachikaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University HospitalMakotoNakanishiDepartment of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityTadashiNinomiyaDepartment of Anatomy, Nihon University School of DentistryShoAkashiDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiKondoDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNorifumiMoritaniDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroKobayashiDivision of Hard Tissue Research, Institute for Oral Science, Matsumoto Dental UniversityTatsuoFujiiDepartment of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversitySeijiIidaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIntermittent parathyroid hormone (PTH) administration is known to promote bone healing after surgical procedures. However, the mechanism and influence of PTH on the mineral and collagen quality of the jaw are not well understood. Most studies have focused on analyzing the bone density and microstructure of the mandible, and have insufficiently investigated its mineral and collagen quality. Oxidative stress activates osteoclasts, produces advanced glycation end products, and worsens mineral and collagen quality. We hypothesized that PTH induces oxidation and affects the mineral and collagen quality of newly formed mandibular bone. To test this, we examined the mineral and collagen quality of newly formed mandibular bone in rats administered PTH, and analyzed serum after intermittent PTH administration to examine the degree of oxidation. PTH administration reduced mineralization and worsened mineral and collagen quality in newly formed bone. In addition, total anti-oxidant capacity in serum was significantly decreased and the oxidative-INDEX was increased among PTH-treated compared to vehicle-treated rats, indicating serum oxidation. In conclusion, intermittent administration of PTH reduced mineral and collagen quality in newly formed mandibular bone. This effect may have been induced by oxidation.No potential conflict of interest relevant to this article was reported.SpandidosActa Medica Okayama1019-64394922016TGF-β in jaw tumor fluids induces RANKL expression in stromal fibroblasts499508ENChiakiYamadaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomonaoAikawaDepartment of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka UniversityEmiOkunoDepartment of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka UniversityKazuakiMiyagawaDepartment of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka UniversityKatsuhikoAmanoDepartment of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka UniversitySosukeTakahataDepartment of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka UniversityMasaakiKimataDepartment of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka UniversityMasayaOkuraDepartment of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka UniversitySeijiIidaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikihikoKogoDepartment of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University Odontogenic tumors and cysts, arising in the jawbones, grow by resorption and destruction of the jawbones. However, mechanisms underlying bone resorption by odontogenic tumors/cysts remain unclear. Odontogenic tumors/cysts comprise odontogenic epithelial cells and stromal fibroblasts, which originate from the developing tooth germ. It has been demonstrated that odontogenic epithelial cells of the developing tooth germ induce osteoclastogenesis to prevent the tooth germ from invading the developing bone to maintain its structure in developing bones. Thus, we hypothesized that odontogenic epithelial cells of odontogenic tumors/cysts induce osteoclast formation, which plays potential roles in tumor/cyst outgrowth into the jawbone. The purpose of this study was to examine osteoclastogenesis by cytokines, focusing on transforming growth factor-β (TGF-β), produced by odontogenic epithelial cells. We observed two pathways for receptor activator of NF-κB ligand (RANKL) induction by keratocystic odontogenic tumor fluid: the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway through interleukin-1α (IL-1α) signaling and non-COX-2/PGE2 pathway through TGF-β receptor signaling. TGF-β1 and IL-1α produced by odontogenic tumors/cysts induced osteoclastogenesis directly in the osteoclast precursor cells and indirectly via increased RANKL induction in the stroma.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7032016Structure of a New Palatal Plate and the Artificial Tongue for Articulation Disorder in a Patient with Subtotal Glossectomy205211ENKen-ichiKozakiDepartment of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShigehisaKawakamiDepartment of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakayukiKonishiDivision of Physical Medicine and Rehabilitation, Okayama University HospitalKeijiOhtaDental Laboratory Division, Okayama University HospitalJitsuroYanoDepartment of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomooOnodaDepartment of Otolaryngology-Head and Neck Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiMatsumotoDepartment of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuyoshiMizukawaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University HospitalYoshihiroKimataDepartment of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazunoriNishizakiDepartment of Otolaryngology-Head and Neck Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeijiIidaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkioGofukuGraduate School of Natural Science and Technology, Okayama UniversityMasanobuAbeDepartment of Computer Science, Okayama UniversityShogoMinagiDepartment of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayama Dream Speech ProjectCase Report10.18926/AMO/54420A palatal augmentation prosthesis (PAP) is used to facilitate improvement in the speech and swallowing functions of patients with tongue resection or tongue movement disorders. However, a PAPʼs effect is limited in cases where articulation disorder is severe due to wide glossectomy and/or segmental mandibulectomy. In this paper, we describe speech outcomes of a patient with an articulation disorder following glossectomy and segmental mandibulectomy. We used a palatal plate (PP) based on a PAP, along with an artificial tongue (KAT). Speech improvement was evaluated by a standardized speech intelligibility test consisting of 100 syllables. The speech intelligibility score was significantly higher when the patient wore both the PP and KAT than when he wore neither (p＝0.013). The conversational intelligibility score was significantly improved with the PP and KAT than without PP and KAT (p＝0.024). These results suggest that speech function can be improved in patients with hard tissue defects with segmental mandibulectomy using both a PP and a KAT. The nature of the design of the PP and that of the KAT will allow these prostheses to address a wide range of tissue defects.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6932015Maxillary Advancement for Unilateral Crossbite in a Patient with Sleep Apnea Syndrome177182ENMitsuhiroHoshijimaTadashiHonjoNorifumiMoritaniSeijiIidaTakashiYamashiroHiroshiKamiokaCase Report10.18926/AMO/53525This article reports the case of a 44-year-old male with skeletal Class III, Angle Class III malocclusion and unilateral crossbite with concerns about obstructive sleep apnea syndrome (OSAS), esthetics and functional problems. To correct the skeletal deformities, the maxilla was anteriorly repositioned by employing LeFort I osteotomy following pre-surgical orthodontic treatment, because a mandibular setback might induce disordered breathing and cause OSAS. After active treatment for 13 months, satisfactory occlusion was achieved and an acceptable facial and oral profile was obtained. In addition, the apnea hypopnea index (AHI) decreased from 18.8 preoperatively to 10.6 postoperatively. Furthermore, after a follow-up period of 7 months, the AHI again significantly decreased from 10.6 to 6.2. In conclusion, surgical advancement of the maxilla using LeFort I osteotomy has proven to be useful in patients with this kind of skeletal malocclusion, while preventing a worsening of the OSAS.No potential conflict of interest relevant to this article was reported.Pergamon-Elsevier Science Ltd.Acta Medica Okayama0003-996959122014Assessment of intraoral mucosal pain induced by the application of capsaicin13341341ENRyujiTerayamaKotaroMaruhamaHirokiTsuchiyaMasahideMizutaniSeijiIidaTomosadaSugimotoObjective
To develop an objective method for assessing nociceptive behaviour in an animal model of capsaicin-induced intraoral pain. Changes in nociceptive responses were also examined after injury to the inferior alveolar nerve (IAN).
Design
Nociceptive responses evoked by the intraoral application of various doses of capsaicin were analyzed in lightly anaesthetized rats. The number of c-Fos protein-like immunoreactive (Fos-LI) neurons in the medullary dorsal horn (MDH) induced by the intraoral application of capsaicin was measured. Behavioural and c-Fos responses were also examined 14 days after injury to the IAN.
Results
Larger doses of intraoral capsaicin (1, 10 and 100 μg) induced vigorous licking behaviour and c-Fos response in the MDH in a reproducible manner. The magnitudes of both behavioural activity and the c-Fos response from the 10 and 100 μg doses of capsaicin were significantly greater than that by the 1 μg dose. Injury to the IAN exaggerated the behavioural and c-Fos responses evoked by intraoral capsaicin.
Conclusions
The intraoral application of capsaicin is a valid and reliable method for studying intraoral pain and hyperalgesia following nerve injury.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama0730-231211552014CCN2 as a Novel Molecule Supporting Energy Metabolism of Chondrocytes854865ENAyaMaeda-UematsuSatoshiKubotaHarumiKawakiKazumiKawataYoshiakiMiyakeTakakoHattoriTakashiNishidaNorifumiMoritaniKaren M.LyonsSeijiIidaMasaharuTakigawaCCN2/connective tissue growth factor (CTGF) is a unique molecule that promotes both chondrocytic differentiation and proliferation through its matricellular interaction with a number of extracellular biomolecules. This apparently contradictory functional property of CCN2 suggests its certain role in basic cellular activities such as energy metabolism, which is required for both proliferation and differentiation. Comparative metabolomic analysis of costal chondrocytes isolated from wild-type and Ccn2-null mice revealed overall impaired metabolism in the latter. Among the numerous metabolites analyzed, stable reduction in the intracellular level of ATP, GTP, CTP, or UTP was observed, indicating a profound role of CCN2 in energy metabolism. Particularly, the cellular level of ATP was decreased by more than 50% in the Ccn2-null chondrocytes. The addition of recombinant CCN2 (rCCN2) to cultured Ccn2-null chondrocytes partly redeemed the cellular ATP level attenuated by Ccn2 deletion. Next, in order to investigate the mechanistic background that mediates the reduction in ATP level in these Ccn2-null chondrocytes, we performed transcriptome analysis. As a result, several metabolism-associated genes were found to have been up-regulated or down-regulated in the mutant mice. Up-regulation of a number of ribosomal protein genes was observed upon Ccn2 deletion, whereas a few genes required for aerobic and anaerobic ATP production were down-regulated in the Ccn2-null chondrocytes. Among such genes, reduction in the expression of the enolase 1 gene was of particular note. These findings uncover a novel functional role of CCN2 as a metabolic supporter in the growth-plate chondrocytes, which is required for skeletogenesis in mammals.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6442010Atypical Lipomatous Tumor of the Tongue:Report of a Case257261ENNorifumiMoritaniTomohiroYamadaKoichiMizobuchiMariWakimotoYokoIkeyaTatsushiMatsumuraKatsuakiMishimaSeijiIidaCase Report10.18926/AMO/40134The term atypical lipomatous tumor (ALT) is synonymous with well-differentiated liposarcoma (WDL). This tumor occurs very rarely in the tongue. Thus, it is difficult to predict its prognosis. Although recurrence of ALT/WDL is thought to be unlikely after complete excision, long-term follow-up is necessary when considering the pathologic conditions of this tumor at other sites. Here, we report a case of an ALT of the tongue, with a review of the literature. A 68-year-old man was referred to our hospital because of a tumor on the left side of his tongue. Upon palpation, the tumor was 12mm in diameter, circumscribed, elastic and hard, well demarcated, movable, and painless. We diagnosed the lesion as a lipoma and extirpated the tumor under local anesthesia. Because the specimen was histopathologically diagnosed as an ALT, as a precaution, we excised an additional 5mm from the area surrounding the original tumor under general anesthesia. Three years after the operation, the tongue demonstrated good healing without paresthesia or dysfunction, and to date there has been no evidence of recurrence.No potential conflict of interest relevant to this article was reported.