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Potential Role of Hedgehog Signaling in Radiation-induced Liver Fibrosis (방사선에 의한 간섬유증에서 헤지호그의 잠재적 역할)

  • Wang, Sihyung;Jung, Youngmi
    • Journal of Life Science
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    • v.23 no.5
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    • pp.710-720
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    • 2013
  • Radiotherapy is commonly used in treating many kinds of cancers which cannot be cured by other therapeutic strategies. However, radiotherapy also induces the damages on the normal tissues. Radiation-induced fibrosis is frequently observed in the patients undergoing radiotherapy, and becomes a major obstacle in the treatment of intrahepatic cancer. Hedgehog (Hh) that is an essential in the liver formation during embryogenesis is not detected in the healthy liver, but activated and modulates the repair process in damaged livers in adult. The expression of Hh increases with the degree of liver damage, regulating the proliferation of hepatic progenitors and hepatic stellate cells (HSC). In addition, Hh induces epithelial-to-mesencymal transition (EMT) and activation of myofibroblasts. In the irradiated livers, up-regulated expression of Hh signaling was associated with proliferation of progenitors, EMT induction, and increased fibrosis. Female-specific expression of Hh leaded to the expansion of progenitors and the accumulation of collagen in the irradiated livers of female mice, indicating that gender disparity in Hh expression may be related with radiation-susceptibility in female. Hence, Hh signaling becomes a novel object of studies for fibrogenesis induced by radiation. However, the absence of the established experimental animal models showing the similar physiopathology with human liver diseases and fibrosis-favorable microenvironment hamper the studies for the radiation-induced fibrosis, providing a few descriptive results. Therefore, further research on the association of Hh with radiation-induced fibrosis can identify the cell and tissue-specific effects of Hh and provides the basic knowledge for underlying mechanisms, contributing to developing therapies for preventing the radiation-induced fibrosis.

The Calcium Release from Cardiac Mitochondria by Sodium and Potassium ($Na^+$$K^+$에 의한 심장근 Mitochondria에서의 $Ca^{++}$ 유리작용)

  • Kim, Myung-Suk
    • The Korean Journal of Pharmacology
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    • v.14 no.1_2
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    • pp.1-11
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    • 1978
  • The $Na^+$-and $K^+$-induced $Ca^{++}$ release was measured isotopically by Milipore filter technique in mitochondria isolated from rabbit ventricles. The release of $Ca^{++}$ from mitochondria could be induced by 1-3 mM of $Na^+$ added in incubating medium under the presence of 0.5mM EGTA to prevent the released $Ca^{++}$ from rebinding with mitochondrial membrane. The amount of $Ca^{++}$ released was increased by increasing the concentration of $Na^+$ added. 100mM $K^+$, in itself, did not induce the $Ca^{++}$ release from cardiac mitochondria, the $Na^+$-induced $Ca^{++}$ release, however, was potentiated by the presence of $K^+$. The potentiation of $Na^+$-induced $Ca^{++}$ release by $K^+$ was proportional to the $Na^+/K^+$ ratio presented in the incubating medium. Among the monovalent cations other than $Na^+$, the release of $Ca^{++}$ from cardiac mitochondria was shared only by $Li^+$. The $Na^+$-induced $Ca^{++}$ release could be also observed in the mitochondria isolated from liver and kidney. However, the $Na^+$ sensitivity was somewhat lower in liver and kidney mitochondria than in heart mitochondria. The release of $Ca^{++}$ induced by $Na^+$ in the mitochondria isolated from the experimentally produced failured heart was not different from that in the normal heart mitochondria, and was not directly modified by $10^{-6}{\sim}10^{-5}$ M of Ouabain. From the experiments, it was suggested that the $Ca^{++}$ released from mitochondria by $Na^+$ could be used in excitation-contraction coupling process to initiate the contraction of the cardiac myofibrils. Futhermore, it appeared that the phenomenon of $Ca^{++}$ release from cardiac mitochondria by $Na^+$ and $K^+$ might be related to the inotropic effect of digitalis glycoside which could bring about the increase of $Na^+$ or the reduction of $K^+$ intracellulary through the inhibition of $Na^+$, $K^+$-ATPase.

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The Immunohistochemical Expression of Collagens and the Morphogenesis in the Developing Mandible of Human Embryos and Fetuses (배자와 태아에서 하악골의 형태발생 및 교원질 발현에 관한 면역조직화학적 연구)

  • Kook, Yoon-Ah;Kim, Sang-Cheol;Kim, Eun-Cheol;Kim, Oh-Hwan;Kim, Jong-Ghee
    • The korean journal of orthodontics
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    • v.26 no.2 s.55
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    • pp.187-196
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    • 1996
  • Underlying malocclusions and dentofacial deformities are often related to variations in the craniofacial development. Type I and type II collagens are considered the major collagens of bone and cartilage respectively. Monitoring the patterns of those protein expressions during development will Provide a basis for the understanding of normal and abnormal growths. This study was undertaken to investigate the morphogenetic changes and the expression patterns of type I and II collagen proteins involved in the developing mandible of human embryos and fetuses. 50 embryos and fetuses were studied with Hematoxylin and Eosin, Alcian, blue-PAS, Masson Trichrome, md Immunohistochemical stains. The results were as follows : 1. A 13.5 mm embryo showed the stomatodeum with dental lamina, maxillary and mandibular processes. Meckel's cartilage appeared in the mandibular arch of a 20.5 mm embryo. New bone formation was bilaterally initiated at the outer side of middle portion of Meckel's cartilage of 22-38 mm embryos. 2. Meckel'cartilage was resorbed at the 15th week fetus. The endochondral ossification was observed where there was direct replacement of cartilage by bone. Meckel'cartilage disappeared and membraneous ossification were observed at the 25th week. 3. Before the appearance of Meckel's cartilage, the expression of type I collagen was moderate at the odontogenic epithelium of maxillary & mandibular process, but mild for the expression of type II collagen. 4. During the appearance of Meckel's cartilage and new bone formation, the immunoactivity of type II collagen was more expressed than type I collagen at the Meckel's cartilage and new bone. 5. During intrarmembranous bone formation, the expression of type II collagen was rare in the bony trabeculae. There was a switch for the expression of collagens from type II to type I during the appearance of Meckel's cartilage.

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Characteristics of Sleep Apnea Syndrome in the Elderly in a Clinical Setting (나이에 따른 수면무호흡증 임상적 특성의 변화)

  • Shin, Yoon-Kyung;Yoon, In-Young;Hong, Min-Chul;Yun, Yong-Don
    • Sleep Medicine and Psychophysiology
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    • v.12 no.1
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    • pp.39-44
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    • 2005
  • Objectives: Much attention has been paid to sleep apnea syndrome (SAS) in the elderly because of its high prevalence. It is expected that SAS in the elderly has both similarities and differences compared to SAS in the young or middle-aged populations. The aim of this study was to elucidate the characteristics and consequences of SAS in the elderly. Methods: In this study we included 210 young or middle-aged adults between 23 and 59 years (20 women and 190 men) and 65 older adults between 60 and 83 years of age (16 women and 49 men). Respiratory disturbance indices (RDIs) of the study subjects were more than 5 in an overnight polysomnography. They completed the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). Informations about body mass index (BMI), neck, waist, and hip measurements, and blood pressure were obtained. Results: No difference was observed between older adults with SAS (older SAS) and adults aged under 60 with SAS (SAS aged under 60) in RDI, apnea index, % time of oxygen saturation less than 90%, and PSQI. Obstructive apnea index and oxygen desaturation index (ODI) were lower in older SAS. Compared to SAS aged under 60, lowest oxygen saturation and central apnea index were higher in older SAS, but they were statistically not significant. BMI and neck circumference were significantly lower in older SAS compared to SAS aged under 60. Diastolic blood pressure was lower in older SAS compared to SAS aged under 60 with no difference in systolic blood pressure. Older SAS showed lower scores in ESS than SAS aged under 60. Significant correlation was observed between RDI and BMI in SAS aged under 60, but not in the case of older SAS. The relationships between RDI and neck circumference, systolic and diastolic pressure, and ESS were similar. Conclusions: The elderly with SAS were not over-weight and there was no relationship between body weight and the severity of SAS. Also, the behavioral and cardiovascular effects of SAS were not marked in the elderly, which might be partly explained by decreased ODI and relatively higher lowest oxygen saturation in older SAS. The normal aging process, aside from increased body weight, might contribute to the development of SAS in the elderly with modest complications.

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Factors Affecting the Weight Control Intention of the Female Adolescent by Body Size - In Daegu Area - (청년기 여성의 체형에 따른 체중조절 행동의도에 영향을 미치는 요인 분석 - 대구지역을 중심으로 -)

  • Ryu, Ho-Kyung
    • The Korean Journal of Community Living Science
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    • v.16 no.4
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    • pp.83-93
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    • 2005
  • This study was conducted to provide information about the behavioral intentions to diet in adolescent females. To explain the behavior intention to diet, a conceptual framework based on the ' Social Support, Control and the Stress Process Model ' and the ' Theory of Reasoned Actio ' was used. The survey was carried out by self-questionnaires with 463 female high school and college students in Daegu. Analysis of data was done by using mean, correlation and multiple regression analysis with the SAS computer program. Subjects were divided into 3 groups-underweight, normal weight, and overweight-according to their current body size. The most powerful influencing factor related to perceived stress -that is dissatisfaction with body image- was the current figure, regardless of current body size. The fatter the current body size, the higher the score for the behavioral intention to diet. In attitude toward the behavior of dieting, the fatter the current figure, the higher the attitude score, and the belief of behavioral outcome was the main decision variable. For the score of the subjective norm, the overweight group was significantly higher than other groups. The influencing factors for the behavioral intention to diet were perceived stress and attitude toward dieting behavior, especially beliefs of behavioral outcome.

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Analysis on the Dosimetric Characteristics of Tangential Breast Intensity Modulated Radiotherapy (유방암의 접선 세기조절 방사선치료 선량 특성 분석)

  • Yoon, Mee Sun;Kim, Yong-Hyeob;Jeong, Jae-Uk;Nam, Taek-Keun;Ahn, Sung-Ja;Chung, Wong-Ki;Song, Ju-Young
    • Progress in Medical Physics
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    • v.23 no.4
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    • pp.219-228
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    • 2012
  • The tangential breast intensity modulated radiotherapy (T-B IMRT) technique, which uses the same tangential fields as conventional 3-dimensional conformal radiotherapy (3D-CRT) plans with physical wedges, was analyzed in terms of the calculated dose distribution feature and dosimetric accuracy of beam delivery during treatment. T-B IMRT plans were prepared for 15 patients with breast cancer who were already treated with conventional 3D-CRT. The homogeneity of the dose distribution to the target volume was improved, and the dose delivered to the normal tissues and critical organs was reduced compared with that in 3D-CRT plans. Quality assurance (QA) plans with the appropriate phantoms were used to analyze the dosimetric accuracy of T-B IMRT. An ionization chamber placed at the hole of an acrylic cylindrical phantom was used for the point dose measurement, and the mean error from the calculated dose was $0.7{\pm}1.4%$. The accuracy of the dose distribution was verified with a 2D diode detector array, and the mean pass rate calculated from the gamma evaluation was $97.3{\pm}2.9%$. We confirmed the advantages of a T-B IMRT in the dose distribution and verified the dosimetric accuracy from the QA performance which should still be regarded as an important process even in the simple technique as T-B IMRT in order to maintain a good quality.

A Study on Antioxidative Effects of Sipyimiguanjungtang and Osuyubujayijungtang, Korean Traditional Prescriptions for Soum Constitutes, in Brain and Liver of Rat (소음인(少陰人) 십이미관중탕(十二味寬中湯), 오수유부자이중탕(吳茱萸附子理中湯)이 흰쥐의 뇌(腦)와 간조직(肝組織)의 항산화(抗酸化) 기전(機轉)에 미치는 영향(影響))

  • Jung, Bong-yeon;Song, Il-byung
    • Journal of Sasang Constitutional Medicine
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    • v.11 no.2
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    • pp.227-250
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    • 1999
  • The free radical theory of aging was introduced in 1956 by Denham Harman. This aging theory proposed that normal aging results from random deleterious damage to tissues by free radical and supplying antioxidant lead to decrease oxidative damage, inhibit aging process. In this study, we investigated antioxidantive effects of four Korean constitutional prescriptions for 'Soum' constitution - Palmulgunjatang(Y1), Sipyimiguanjungtang(Y2), Osuyubujayijungtang(Y3) and Seungyangyikkibujatang(Y4). Antioxidative activity of this prescriptions was examined by 1,1-diphenyl-2-picrylhyrdazyl radicals, superoxide anion radicals, peroxyl radical, hydroxyl radical scavenging effects and erythrocyte hemolysis inhibitory effects. Y2 and Y3 were shown to have relatively high antioxidative activity on this methods. In additions, result of the cytoprotective effects of Korean constitutional prescriptions agianst 2,2'-azobis(amidinopropane) dihydrochloride (AAPH), a free radical initiator, induced cytotoxcity in human hepatoblastoma cell line was similarly obtained. On the basis of this result, we assayed the antioxidative effects of Y2 and Y3 on experimental oxidative damage, induced in mouse by 100mg/kg AAPH. Male ICR mouse were given oral administration of 500mg/kg Y2 and Y3 for 4 weeks. Thiobarbuturic acid reactive substance (TBARS) and protein degradation level in liver, plasma and brain as index of oxidative damage were decreased and thiol compound, total antioxidant status in plasma were increased by Y2 administration. But, Y3 injected group was decreased only protein degradation level in brain. Also, glutathione, a potent water-soluble endogenous antioxidant, concentration was increased by Y2 and Y3 administration in liver and brain. However, superoxide dismutase and catalase activity as a major antioxidative enzyme in vivo were not shown change by Y2 and Y3 administration. On the basis of these result, Y2 have an antioxidative effects on both water-soluble fraction and lipid-solube fraction in cell and tissues. But, Y3 has a lower antioxidative effects on lipid-soluble fraction than Y2 in cell and tissues. These results suggest that Y2 has a antioxidative effects by protect the tissue against oxygen free radical mediated oxidative damage and Y3 has a limited antioxidaitve effects on water-soluble fraction in vivo. Therefore, we make report that Y2 is more effective prescriptions for anti-aging or therapeutics of diseases.

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호스피스와 종교적 죽음이해

  • Sin, Min-Seon;Kim, Mun-Su
    • Korean Journal of Hospice Care
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    • v.6 no.1
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    • pp.1-11
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    • 2006
  • There are various understandings how to define death. In the context of medicine, death is defined as the irreversible change of the tissue according to the cessation of circulation and respiration. According to the psychologists, a person need to accept the finiteness as a human being and remain conscious that the death is not avoidable. And they say if a person doesn't regard death as unavoidable reality of life he or she will not confront the humanistic death and after all will die like animals. In philosophy, death is viewed as an unwelcome reality in the end of the journey of life. Sociologists usually understand that the society is the organization composed with living persons and human beings which construct and transmit the culture from generation to generation between the both ends of life and death. In society, the generation is changed, maintained, and developed through the phenomenon of death. Although death of human being is natural event in society, the death of a specific person brings a sense of loss, crisis, and anxiety to the communities like family, regional society, nation, and the world. In this context, death is not confined to personal dimension and it can be regarded as a social problem. It is valuable to summarize the religious perspectives on the meaning of death for the better hospice care. In shamanism, there are basic idea that although the flesh of human being disappears, soul never die. If human dies, the flesh of human being disappears but soul never disappear and come back to the origin of soul as it is called chaos. So in shamanism, it is said that shaman can solve the mortified feeling, restore the broken harmony, send the soul to comfortable space- the origin, and guarantee the blessing of descendents. Buddhists regard the death as an essential component through the cycles of life. Through this cycle, human being exits as an endlessly transmigrating being and the death is just a restoration to the original status. In Confucianism, the view on the death based on the philosophy of the "Yin and Yang" and "Five elements". In Buddhist tradition, many believers said the philosophy of "Death is the same as life". Unlike usual thoughts that a god governs "life and death" and "fortune and misfortune", Confucianists deny the governance of a god and emphasize the natural orders in which every phenomenon in the world moves according to the principle. Confucianists understand the death as a natural order with this principle. In Confucianists' belief, the essence of human being remains in their own descendent's lives after the death of ancestor, so in Confucianism there is no concept of immortality of the soul. In the history of Christianity, death has been defined generally as the separation of the immortal soul from the mortal body. In the earlier days of Old Testament, the death is regarded as a disappearance of just a flesh and human never disappear and always live in the relationship with God. Later days in Old Testament, we can find the growing concern for the life after the death because of the entrance of the theodicy. In the New Testament, the death is not regarded as the normal process of the human life and regarded as the abnormal status in which death come to human because of sin as a decisive factor and it should be conquered. In fact, the most of us afraid death because not of the fear of death itself but of the sense of the emptiness and regrets. so many people often make the monument hoping to live forever. But Christian usually regard this behavior as a sinful act because human being usually think themselves as a master of their life and attempt to become immortal in this kind of trial mortal. But if we live with God, we cannot confront such a condition because we aware limits as a mortal human being and entrust everything on Him and want to live according to His guidance. Therefore, in the Christian tradition, the death is regarded as accomplishment of life, fruits of life, invitation to the eternal life, and the last stage of human growth. For human being, the death is the great step of maturation as a human in the final stage of life.

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Adhesion-induced generation of oxygen free radical from human alveolar macrophages and its mechanisms (폐포대식세포의 부착에 의한 산소유리기 분비능 활성화 및 그 기전)

  • Chung, Man-Pyo;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo;Han, Yong-Chol
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.2
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    • pp.210-220
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    • 1996
  • Background : Neutrophils or monocytes separated in vitro by the adherence to plastic surface are known to be activated by surface adherence itself and subsequent experimental data might be altered by surface adherence. In the process of surface adherence, adhesion molecules have a clear role in intracellular signal pathway of cellular activation. Human alveolar macrophages(HAM) are frequently purified by the adherence procedure after bronchoalveolar lavage. But the experimental data of many reports about alveolar macrophages have ignored the possibility of adhesion-induced cellular activation. Method : Bronchoalveolar lavage was performed in the person whose lung of either side was confirmed to be normal by chest CT. With the measurement of hydrogen peroxide release from adherent HAM to plastic surface and non-adherent HAM with or without additional stimulation of phorbol myristate acetate(PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP), we observed the effect of the adherence to plastic surface. We also evaluated the effect of various biological surfaces on adhesion-induced activation of HAM. Then, to define the intracellular pathway of signal transduction, pretreatment with cycloheximide, pertussis toxin and anti-CD11/CD18 monoclonal antibody was done and we measured hydrogen peroxide in the culture supernatant of HAM. Results : 1) The adherence itself to plastic surface directly stimulated hydrogen peroxide release from human alveolar macrophages and chemical stimuli such as phorbol myristate acetate(PMA) or N-formyl-methionyl-leucyl-phenylalanine(fMLP) colud not increase hydrogen peroxide release in these adherent macrophages which is already activated. 2) PMA activated human alveolar macrophages irrespective of the state of adhesion. However, fMLP stimulated the release of hydrogen peroxide from the adherent macrophages, but not from the non-adherent macrophages. 3) HAM adherent to A549 cell(type II alveolar epithelium-like human cell line) monolayer released more hydrogen peroxide in response to both PMA and fMLP. This adherence-dependent effect of fMLP was blocked by pretreatment of macrophages with cycloheximide, pertussis toxin and anti-CD18 monoclonal antibody, Conclusion : These results suggest that the stimulatory effect of PMA and fMLP can not be found in adherent macrophage because of the activation of human alveolar macrophage by the adherence to plastic surface and the cells adhered to biologic surface such as alveolar epithelial cells are appropriately responsive to these stimuli. It is also likely that the effect of fMLP on the adherent macrophage requires new protein synthesis via G protein pathway and is dependent on the adhesion between alveolar macrophages and alveolar epithelial cells by virtue of CD11/CD18 adhesion molecules.

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EFFECT OF THE NUCLEAR FACTOR I-C ON THE FORMATION OF HERTWIG'S EPITHELIAL ROOT SHEATH DURING ROOT DEVELOPMENT (Nuclear factor I-C가 치근발생 과정에서 Hertwig's 상피초 형성에 미치는 영향)

  • Shin, In-Cheol;Park, Joo-Cheol;Jeong, Moon-Jin;Oh, Hyun-Ju;Park, Sun-Hwa;Lee, Chang-Seop;Kim, Heung-Joong
    • Journal of the korean academy of Pediatric Dentistry
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    • v.32 no.3
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    • pp.576-583
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    • 2005
  • Tooth formation is a complex developmental process that is mediated through a series of reciprocal epithelial-mesenchymal interactions. Several signal pathways and transcription factors have been implicated in regulating molar crown development, but relatively little is known about the regulation of root development. It was reported that NFI-C knockout mice showed abnormal root formation with normal crown. The aims of this study are to elucidate how the NFI-C regulate the determine of root shape and odontoblasts differentiation. We carried out immunohistochemistry using cytokeratin to investigate the role of Hertwig's epithelial root sheath and DSPP mRNA in-situ hybridization to conform the nature of root dentin during root development in NFI-C knockout mice. Cytokeratin reacted with all the HERS cells and the continuity of cytokeratin positive cells between the HERS cells and enamel epithelium was lost in the cervical region both wild and K/O types. After root dentin deposition cytokeratin positive-HERS cells showed irregularity and loss of polarity in the cervical region in K/O type. DSPP mRNA was strongly expressed in odontoblasts of crown and root dentin in wild type mice, whereas expression of DSPP mRNA was restricted in odontoblast of crown dentin in the K/O type. During root formation in NFI-C knockout mice, HERS normally grow out of the crown but fail to induce odontoblast differentiation in root portion. These results suggest that NFI-C may play important roles in odontoblast differentiation during root dentin formation.

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