1'0 determine Lhe ll1echanism of cell c1eath incluced by iron chelators. we explored the pathways of the three structurally relatecl ll1 itogen-activatecl protein(MAP) kinase subfami li esduring iron cbelator- inclucecl apoptosis ancl differentiation of oral precancerous ancl cancel‘ cells. The iron chelator c1 eferoxamine(DFO) exertecl potent timeancl c1ose-c1epenclent inhi bitory effects on the growth of IHOK and HN4 cells The major mechanism of growth inhibition following DFO treatment was fOllncl to be apoptosis incluction. as assessecl by annexin V-FITC staining. cell cycle analysis‘ DNA lacldering, a ncl Hoechst staining. We report that DF'O s trongly activates the p38 MAP kinase and extracell ular signal- regu lated kinase(ERK). but c10es not activate the c-Jun N-terminal kin ase/ stl않s-activaLecl protein kinase(JNK/8APK) . Of the three MAP kinase blockers usecl‘ the selective p38 MAP kinase inhibitor 8ß203580 ancl ERK inhibitor PD98059 protected oral premaIignant ancl malignant cells againsL iron chelator- nclllced cell death. which incl icates that the p38 MAP kinase serves as a major mecliator 01' apoptos is induced by this iron chelator DFO also evoked the release of cytochrome c from mitochondria, and incluced the activation of caspase-3 ancl caspase-8 in oral cancer cells, which suggests that apoptosis occurs via the mi tochoncl ri on - mecl iaLed pathway. DFO enhanced the expression of Bax in IHOK ancl HN4 cells. consistent witll thei r p53 status Moreover. DFO downregulatecl the expression 01' Bcl-2 in oral cancer cells. which suggests that DFO- incluced apoptos is 01' oraJ cancer and precancerous cells may be mediatecl by an increase in the ratio of pro-apoptotic to anti-apoptotic proteins. ln terestingJy, trcatmcnt 01' IHOK ancl HN4 cel ls with 8B203580 abolishecl cytochrome c release‘ as wel l as the activation of caspase-3 and caspase-8. DFO suppressecl the expression of epithelial di ffe rentiation markers, such as involucrin, t ransglutaminase II. CK6. and CK19. ancl this suppression was blockecl by p38 ancl ERK MAP kinase ll1hlbltors The oral premalignant(IHOK) ancl malignant cell s(I-lN4) showed differential responses to DFO with respect to the expression of cel l cycle regulatory proteins. cell growth. ancl apoptosis. Coll ectively. the current study reveals that p38 MAP kinase plays an ill1 portant role in iron chela tor-mecliatecl cel l cleath and in the suppression of differentiation of oral premalignantandmalignanLcell s.by activating a c10wnstream apoptotic cascade that executes the ceIl c1eath pathway

The phylogeneticall y conserved nuclear factor 1 (NFI) gene fami ly encodes s ite-specific tra nscription factors essential for the development of a number of organ syst ems. There are four NFI genes in mamma ls (Nfi a , Nfib, Nfi c, and Nfix) and single NFI genes in Drosophila melanogaster, Caenorhabdi t is elegans, Anopheles spP. ‘ and other simpl e animals. It was reported that Nfia-defici ent mice exhi bit agenesis of the corpus call osum and other forebrain defects , wher eas Nfib-defi cient mice possess unique defects in lung ma turation and fo rebrain defect. Recently, it was also found that Nfic-defi cient mice exhibit agenesis of mo l ar서 roots and severe incisor defects. In the present study, we investigat ed the possible role of NFI-C in odon toblast diffe rent ia tion and root dentin formation using the innovative and invalua ble Nfic knockout mice model Nfi c-defi cient mice showed a berrant odontoblast differentiation and consequentl y abnormal dentin formation, while other t issues/organs in the body including ameloblasts of the enamel organ a ppeared to be unaffec ted and normal One of the most st r iking changes observed in these aberrant odontoblasts was t he absence of in tercellular junctions beLween them, r esulting in di ssociation of the cells and loss of th eir cellular polarity a nd organi zation. Surprisingly, these cells became trapped in dentin-like minerali zed t issue and thus their overa ll morphology r esembled osteoblasts and os t eocyt es. There was also an increased apoptotic activity in Nfic-deficient mice. These findings strongly s uggest ed that NFI -C plays a key role in odon tob last differentiation and survival in a cell type-specific manner.

정서를 경험하는 동안 자율신경 반응과 외현적 반응, 그리고 얼굴 표정, 몸짓, 자세, 언어 등과 같은 정서적 의사소통을 나타낸다. 안면근육반응은 공포, 놀람, 행복, 혐오, 슬픔, 분노와 같은 감정적인 표현을 측정하는 하나의 수단으로, 특정한 안면근육에 기초를 둔 반응을 식별할 수 있다. 본 연구에서는 아동이 긍정정서와 부정정서를 느낄 때 나타나는 안면근육반응의 변화를 알아보고, 아동이 느끼는 긍정정서와 부정정서의 구분이 가능한지를 알고자 하였다. 시청각 동영상(Audiovisual Film Clips)을 이용하여 긍정정서 (기쁨)와 부정정서를 유발하였고, 47명의 아동이 이들 정서를 느끼는 동안 안면근전도(Facial EMG : 우측 corrugator supercilii와 orbicularis oris)를 측정하였다. 또한 아동이 경험한 정서의 심리반응 결과를 평가하기 위하여 정서평가척도를 사용하였다. 두 정서에 대한 높은 적합성(85%이상)과 효과성(기쁨 3.15, 공포4.4, 5점 만점)을 보였다. 안면근육반응 결과, 두 정서 모두에서 안정상태와 정서 상태간의 유의한 차이가 있었다. 정서에 따른 반응 결과, 긍정정서와 부정정서에 따라 corrugator supercilii와 orbicularis oris 반응의 차이가 나타났다. corrugator supercilii는 긍정정서일 때 부정정서보다 근육의 활동이 더 증가하였다. orbicularis oris는 부정정서일 때 긍정정서보다 근육의 반응이 더 증가하였다.

Nuclear factor 1 (NFI) was discovered as a protein required for adenovirus DNA replication in vitro, but it is now clear that NFI protein plays an important role in the expression of many cellular genes. NFI-C null mice demonstrated aberrant odontoblast differentiation, abnormal dentin formation, and thus molar lacking roots while other tissues/or gans in the body, including ameloblasts appear to be unaffected and normal. However, little is known about the mechanism of NFI -C function in odontoblast differentiation and dentin formation. In this study, in order to elucidate the molecular mechanisms of odntoblast differentiation, we examined morphological characteristics of the aberrant odontoblast in NFI-C null mice. we also evaluate the expression of dentin sialophosphoprotein (DSPP) and bone sialoprotein (BSP) mRNAs in the MDPC-23 cells by northern analysis after over-expression and inactiγation of NFI -C into mouse MDPC-23 cells Odontoblasts of the NFI-C null mouse were round in shape, lost their polarity, organized as a sheet of cells, and trapped in osteodentin-like mineralized tissue. Abnormal odontoblasts of NFI-C null mouse revealed the absence of an intercellular junctional complex known as the t erminal webs. MDPC-23 cells started to express DSPP mRNA beginning from the postnatal day of 14 and showed a steady increase as differentiating into odontoblasts. Over-expression of NFI -C increased the expression of DSPP mRNA. Inactivation of NFI - C induced BSP mRNA expression. These results suggest that NFI-C plays an important role in odontoblast differentiation in a cell-type specific manner and thus in dentin formation

Periodontalligament (PDL) fibroblasts have an ectomesenchymal origin and are known to participate not only in formation of PDL but also in the repair and regeneration of the a이acent alveolar bone and cementum. However, little is known about the molecular mechanism which is related to the development and differentiation of PDL cells. Recendy, we reported the PDLs (a periodontalligament-specific) 22 as a PDL fibroblast-specific mRNA which is not expressed in gingival fibroblasts. In this study, to examine the expression and functional characterization of PDμ22 mRNA and prαein in development and differentiation of periodontal 따sue ， we carried out northem analysis, insitu hybridization, immunofluorescence and immunohistochemistry. The expression of PDLs22 mRNA was increased with PDL cell differentiation from the confluent to multilayer stage but decreased slighdy with mineralized nodule formation in vitro. πle PDLs22 protein was localized on the nuclear membrane and expressed throughout the differentiation of PDL fibroblasts in vitro. The PDLs22 mRNA and protein were expressed in the differentiating cementoblasts, PDL fibroblasts and osteoblasts along the r∞t surface and alveolar bone of the developing rat teeth. These results indicate that the PDLs22 plays an irnportant role in the differentiation of cementoblasts and osteoblasts and thus homeostasis of cementum, PDL and alveolar bone.

Bisphosphonates have been widely used to treat metabolic bone diseases, although the . mechanism of bisphosphonate action on bone has not been fully understood. This study aimed to examine the direct action of pamidronate on cell proliferation and differentiation of cultured human mesenchymal stem cells(hMSC). Four experimental groups and two control groups were designed; Experimental groups included both osteogenic supplement(OS) and pamidronate-treated group, pamidronate-treated group after 1 week OS treatment, only pamidronate-treated group, OS-treated group after 1week pamidronate treatrnent. Control gr。니ps included DMEMtreated group and OS-treated group. Human MSCs were isolate from bone maπow ， and cultured for 7, 14, 21 days. For the detection of osteoblastic differentiation, AI.Pase activity was measured and the expression of type 1 collagen and osteocalcin were evaluated. Von Kossa’s silver stain was performed for the examination of calcification. As results, the proliferation rate of 바1SC was maintained to be more than 90% by 1uglml of pamidronate. AI.Pase activity showed the highest value at the concentration of 100nglml of pamidronate. In pamidronate-treated group, ALPase activity reached a peak at the third week and the expression of type 1 collagen mRNA and protein was enhanced compared to other experimental and control groups, whereas osteocalcin expression was found only in OStreated group. Calcification was decreased by a dose dependent manner followed by pamidronate treatment. This study su잃，est that pamidronate treatrnent may be able to enhance the osteoblastic differentiation of hMSC at the early stage. On the other hand, calcification appeared to be inhibited by pamidronate treatrnent.