RESUMEN
Calcineurin inhibitors (CNIs) have been used off-label for the treatment of refractory Kawasaki disease (KD). However, it remains unknown whether CNIs show protective effects against the development of coronary artery lesions in KD patients. To investigate the effects of CNIs on coronary arteries and the mechanisms of their actions on coronary arteritis in a mouse model of KD, we performed experiments with FK565, a ligand of nucleotide-binding oligomerization domain-containing protein 1 (NOD1) in wild-type, severe combined immunodeficiency (SCID), caspase-associated recruitment domain 9 (CARD9)-/- and myeloid differentiation primary response gene 88 (MyD88)-/- mice. We also performed in-vitro studies with vascular and monocytic cells and vascular tissues. A histopathological analysis showed that both cyclosporin A and tacrolimus exacerbated the NOD1-mediated coronary arteritis in a dose-dependent manner. Cyclosporin A induced the exacerbation of coronary arteritis in mice only in high doses, while tacrolimus exacerbated it within the therapeutic range in humans. Similar effects were obtained in SCID and CARD9-/- mice but not in MyD88-/- mice. CNIs enhanced the expression of adhesion molecules by endothelial cells and the cytokine secretion by monocytic cells in our KD model. These data indicated that both vascular and monocytic cells were involved in the exacerbation of coronary arteritis. Activation of MyD88-dependent inflammatory signals in both vascular cells and macrophages appears to contribute to their adverse effects. Particular attention should be paid to the development of coronary artery lesions when using CNIs to treat refractory KD.
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Arteritis/tratamiento farmacológico , Inhibidores de la Calcineurina/uso terapéutico , Endotelio Vascular/efectos de los fármacos , Macrófagos/efectos de los fármacos , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Factor 88 de Diferenciación Mieloide/metabolismo , Oligopéptidos/uso terapéutico , Animales , Proteínas Adaptadoras de Señalización CARD/genética , Vasos Coronarios/patología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Endotelio Vascular/inmunología , Humanos , Mediadores de Inflamación/metabolismo , Macrófagos/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones SCID , Factor 88 de Diferenciación Mieloide/genética , Células RAW 264.7 , Transducción de SeñalRESUMEN
We have detected DNA polymerase beta (Polß), known as a key nuclear base excision repair (BER) protein, in mitochondrial protein extracts derived from mammalian tissue and cells. Manipulation of the N-terminal sequence affected the amount of Polß in the mitochondria. Using Polß fragments, mitochondrion-specific protein partners were identified, with the interactors functioning mainly in DNA maintenance and mitochondrial import. Of particular interest was the identification of the proteins TWINKLE, SSBP1, and TFAM, all of which are mitochondrion-specific DNA effectors and are known to function in the nucleoid. Polß directly interacted functionally with the mitochondrial helicase TWINKLE. Human kidney cells with Polß knockout (KO) had higher endogenous mitochondrial DNA (mtDNA) damage. Mitochondrial extracts derived from heterozygous Polß mouse tissue and KO cells had lower nucleotide incorporation activity. Mouse-derived Polß null fibroblasts had severely affected metabolic parameters. Indeed, gene knockout of Polß caused mitochondrial dysfunction, including reduced membrane potential and mitochondrial content. We show that Polß is a mitochondrial polymerase involved in mtDNA maintenance and is required for mitochondrial homeostasis.
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LKB1/STK11 is a tumor suppressor gene responsible for Peutz-Jeghers syndrome, an inherited cancer disorder associated with genome instability. The LKB1 protein functions in the regulation of cell proliferation, polarization and differentiation. Here, we suggest a role of LKB1 in non-homologous end joining (NHEJ), a major DNA double-strand break (DSB) repair pathway. LKB1 localized to DNA ends upon the generation of micro-irradiation and I-SceI endonuclease-induced DSBs. LKB1 inactivation either by RNA interference or by kinase-dead mutation compromised NHEJ-mediated DNA repair by suppressing the accumulation of BRM, a catalytic subunit of the SWI/SNF complex, at DSB sites, which promotes the recruitment of an essential NHEJ factor, KU70. AMPK2, a major substrate of LKB1 and a histone H2B kinase, was recruited to DSBs in an LKB1-dependent manner. AMPK2 depletion and a mutation of H2B that disrupted the AMPK2 phoshorylation site impaired KU70 and BRM recruitment to DSB sites. LKB1 depletion induced the formation of chromosome breaks and radials. These results suggest that LKB1-AMPK signaling controls NHEJ and contributes to genome stability.
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Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Reparación del ADN por Unión de Extremidades , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Quinasas de la Proteína-Quinasa Activada por el AMP , Línea Celular Tumoral , Ensamble y Desensamble de Cromatina , Genes Supresores de Tumor , Inestabilidad Genómica , Humanos , Transducción de Señal , TransfecciónRESUMEN
We report a case in which identification of a deceased individual was established using multiple lot numbers printed on a body implantable device. Autopsy of an unknown woman revealed an intramedullary nail inserted within her right femur. The device manufacturer was identified from the configuration of the intramedullary nail, and the "use history" was traced from lot numbers printed on the device's multiple parts. The deceased individual was thus identified as a woman who had attempted suicide by jumping from a height about a year previously and had been transported to a hospital and undergone surgery that included implantation of the intramedullary nail. The main factor contributing to the rapid identification was the manufacturer's and distributor's record of the use history (traceability) of the product, because of their accountability for purposes of quality control. A second contributing factor was multiple lot numbers, resulting in extremely low probability of the same combination of lot numbers being present in multiple individuals. This case confirmed the utility of multiple lot numbers of body implantable devices in forensic identification.
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Clavos Ortopédicos , Etiquetado de Productos , Adulto , Femenino , Fémur/lesiones , Fémur/cirugía , Patologia Forense , Fijación Intramedular de Fracturas/instrumentación , HumanosRESUMEN
We have developed a Si opt-neural probe with multiple waveguides and metal cover for highly accurate optical stimulation. This neural probe had 16 recording sites, three optical waveguides, and metal cover for suppressing light leakage. We evaluated electrochemical properties of the recording sites, and confirmed that the neural probe had suitable characteristics for neural recording. We also demonstrated the optical stimulation to the neurons expressing ChR2 using our probe. As a result, we succeeded multisite optical stimulation, and observed that no light leakage from the optical waveguides because of the metal cover. From in vivo experiments, we successfully recorded optically modulated local field potential using the fabricated Si neural probe with optical waveguides. Moreover, we applied current source density analysis to the recorded LFPs. As a result, we confirmed that light induced membrane current sink in locally stimulated area. Our Si opto-neural probe with multiple optical waveguides and metal-cover is one of the most versatile tools for optogenetics.
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Luz , Metales/química , Neuronas/fisiología , Optogenética/métodos , Estimulación Luminosa , Silicio/química , Potenciales de Acción/fisiología , Animales , Encéfalo/fisiología , Impedancia Eléctrica , Electricidad , Técnicas Electroquímicas , Electrodos , Microtecnología , Neuronas/efectos de la radiación , Ratas TransgénicasRESUMEN
The reduced transition probability B(E2;0(gs)(+)â2(1)(+)) for (28)S was obtained experimentally using Coulomb excitation at 53 MeV/nucleon. The resultant B(E2) value 181(31) e(2)fm(4) is smaller than the expectation based on empirical B(E2) systematics. The double ratio |M(n)/M(p)|/(N/Z) of the 0(gs)(+)â2(1)(+) transition in (28)S was determined to be 1.9(2) by evaluating the M(n) value from the known B(E2) value of the mirror nucleus (28)Mg, showing the hindrance of proton collectivity relative to that of neutrons. These results indicate the emergence of the magic number Z=16 in the |T(z)|=2 nucleus (28)S.
RESUMEN
OBJECTIVES: The aim of this study was to develop and validate a bedside test for executive function in patients with idiopathic normal pressure hydrocephalus (INPH). MATERIALS AND METHODS: Twenty consecutive patients with INPH and 20 patients with Alzheimer's disease (AD) were enrolled in this study. We developed the counting-backward test for evaluating executive function in patients with INPH. Two indices that are considered to be reflective of the attention deficits and response suppression underlying executive dysfunction in INPH were calculated: the first-error score and the reverse-effect index. Performance on both the counting-backward test and standard neuropsychological tests for executive function was assessed in INPH and AD patients. RESULTS: The first-error score, reverse-effect index and the scores from the standard neuropsychological tests for executive function were significantly lower for individuals in the INPH group than in the AD group. The two indices for the counting-backward test in the INPH group were strongly correlated with the total scores for Frontal Assessment Battery and Phonemic Verbal Fluency. The first-error score was also significantly correlated with the error rate of the Stroop colour-word test and the score of the go/no-go test. In addition, we found that the first-error score highly distinguished patients with INPH from those with AD using these tests. CONCLUSION: The counting-backward test is useful for evaluating executive dysfunction in INPH and for differentiating between INPH and AD patients. In particular, the first-error score may reflect deficits in the response suppression related to executive dysfunction in INPH.
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Trastornos del Conocimiento/etiología , Función Ejecutiva/fisiología , Hidrocéfalo Normotenso/complicaciones , Matemática , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/complicaciones , Trastornos del Conocimiento/diagnóstico , Femenino , Trastornos Neurológicos de la Marcha/etiología , Humanos , Hidrocéfalo Normotenso/cirugía , Masculino , Pruebas Neuropsicológicas , Complicaciones Posoperatorias/fisiopatología , Curva ROC , Enfermedades de la Vejiga Urinaria/etiologíaRESUMEN
Reversible posterior leukoencephalopathy syndrome (RPLS) is a distinctive clinicoradiological entity observed in a variety of clinical settings. Cyclosporine (CyA)-RPLS has been reported in a few patients with focal segmental glomerulosclerosis (FSGS); however, there had been no reports on developed RPLS after the re-administration of CyA treatment. We report two patients with FSGS who developed CyA-induced RPLS and summarize the results of a literature review for similar patients. The two patients with FSGS presented here were a 4-year-old boy and a 9-year-old boy, who presented with steroid-resistant nephrotic syndrome (NS) and were treated with CyA. The first patient developed CyA-induced RPLS at the 7th day after the start of CyA treatment, and the second patient at the 16th day after the re-start of CyA treatment. The two patients complained of a visual disorder and exhibited signs of a disturbance in consciousness and hypertension. Electroencephalography (EEG) examinations revealed a generalized slow wave pattern, and magnetic resonance imaging (MRI) disclosed an area of high signal intensity in the white matter. Subsequently, CyA was discontinued and neurological symptoms improved and recrudescence of RPLS did not occur. Our findings suggest that patients with FSGS and NS who are treated with CyA should be closely monitored for the possible onset of RPLS, presenting as a disturbance in consciousness, visual disturbances and/or convulsions.
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Ciclosporina/efectos adversos , Glomeruloesclerosis Focal y Segmentaria/complicaciones , Síndrome de Leucoencefalopatía Posterior/inducido químicamente , Niño , Preescolar , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Humanos , Masculino , Síndrome de Leucoencefalopatía Posterior/diagnósticoRESUMEN
We report on the first spectroscopic study of the N=22 nucleus 32Ne at the newly completed RIKEN Radioactive Ion Beam Factory. A single gamma-ray line with an energy of 722(9) keV was observed in both inelastic scattering of a 226 MeV/u 32Ne beam on a carbon target and proton removal from 33Na at 245 MeV/u. This transition is assigned to the deexcitation of the first Jpi=2+ state in 32Ne to the 0+ ground state. Interpreted through comparison with state-of-the-art shell-model calculations, the low excitation energy demonstrates that the "island of inversion" extends to at least N=22 for the Ne isotopes.
RESUMEN
The structure of neutron-rich isotopes 60Cr and 62Cr was studied via proton inelastic scattering in inverse kinematics. The deformation lengths (delta) for 60Cr and 62Cr were extracted as 1.12(16) and 1.36(14) fm, respectively, providing evidence for enhanced collectivity in these nuclei. An excited state at 1180(10) keV in 62Cr was identified for the first time. We adopted 4;{+} as its spin and parity, leading to the rapid increase of the Ex(4;{+})/E_{x}(2;{+}) ratio, which indicates the development of large deformation in 62Cr near N=40. Importance of the admixture of the gd-shell component above N=40 is also discussed by comparing with a modern shell model calculation.
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AIMS: Interaction of vascular and metabolic factors appears to contribute to the pathogenesis of diabetic neuropathy. The aim of the study was to assess the impact of arterial stiffening and thickness on diabetic neuropathy in Type 2 diabetes. METHODS: In 294 patients with Type 2 diabetes, neuropathy was assessed by four components: the presence of neuropathic symptoms, the absence of ankle tendon reflexes, perception of vibration scores and heart rate variation. We measured intima-media thickness (IMT) of carotid arteries to assess arterial thickening, and brachial-ankle pulse-wave velocity (PWV) and brachial pulse pressure (PP) which reflect arterial stiffening. RESULTS: Diabetic neuropathy, defined as > or = two of the four components, was significantly associated with age, duration, glycated haemoglobin (HbA(1c)), systolic blood pressure, diastolic blood pressure, PP, hypertension, retinopathy, urinary albumin excretion rate, nephropathy stages, PWV and IMT. PWV and PP were significantly associated with neuropathy independent of conventional cardiovascular risk factors. Multiple logistic regression analysis revealed that PWV, retinopathy, age, and HbA(1c), were significant independent determinants of neuropathy. CONCLUSIONS: The present cross-sectional study indicates that markers for vascular wall properties such as PWV, IMT and PP are significantly associated with diabetic neuropathy. PWV and PP are significant determinants of neuropathy independent of conventional cardiovascular risk factors. Multifactorial intervention to inhibit progression of the atherosclerotic process may slow progression of neuropathy.
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Arteriosclerosis/fisiopatología , Diabetes Mellitus Tipo 2/complicaciones , Neuropatías Diabéticas/fisiopatología , Túnica Íntima/diagnóstico por imagen , Túnica Media/diagnóstico por imagen , Anciano , Albuminuria/fisiopatología , Arteriosclerosis/etiología , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/fisiopatología , Estudios Transversales , Neuropatías Diabéticas/diagnóstico por imagen , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factores de Riesgo , UltrasonografíaRESUMEN
To investigate the effect of metabolic syndrome (MS) components on early atherosclerosis markers, i.e., urinary albumin excretion rate (UAE), pulse wave velocity (PWV), and carotid intima-media thickness (IMT), we studied 536 Japanese patients with type 2 diabetes without cardiovascular disease or nephropathy. The MS definition by ATP III was employed. UAE, PWV, and IMT increased significantly with increasing the number of components even before fulfilling the diagnosis of MS. UAE was significantly influenced by high blood pressure, high triglycerides, and low HDL cholesterol. PWV was significantly increased by high blood pressure. IMT was significantly increased by high blood pressure and abdominal obesity. Multiple regression analysis, including MS components and putative risk factors, indicated that the number of MS components, age and glycosylated HbA1C were independent determinants of UAE, PWV, and IMT. LDL cholesterol and male gender were independent determinants of IMT. In conclusion, UAE, PWV, and IMT increased according to increasing the number of MS in type 2 diabetic patients without cardiovascular disease or diabetic nephropathy. The current observation considering the modifiable factors may help to identify patients who are at high risk of experiencing cardiovascular disease.
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Aterosclerosis/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/fisiopatología , Síndrome Metabólico/fisiopatología , Adulto , Anciano , Albuminuria , Aterosclerosis/epidemiología , Angiopatías Diabéticas/epidemiología , Nefropatías Diabéticas , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipertensión/epidemiología , Japón , Masculino , Persona de Mediana Edad , Valores de Referencia , Factores de Riesgo , Triglicéridos/sangreRESUMEN
OBJECTIVE: Lansoprazole and tacrolimus are substrates of ATP binding cassette (ABC) transporters such as P-glycoprotein (ABCBI/multidrug resistance 1) and cytochrome P450 (CYP). The purpose of this study was to investigate the implication of the ABCB1 C3435Tpolymorphism on the pharmacokinetics of (R)-lansoprazole, the major enantiomer, in CYP2C19 extensive metabolizers (EMs) and on gastroesophageal symptoms in renal transplant recipients receiving tacrolimus. MATERIALS: 24 recipients who were CYP2C19 EMs were studied. METHODS: Oral administration of 30 mg lansoprazole was started 2 days before transplantation. On Day 2 before and Day 28 after transplantation, the plasma concentrations of (R)-lansoprazole and tacrolimus were measured. RESULTS: Pretransplantation, there were no significant differences in the pharmacokinetic parameters of (R)-lansoprazole between the 3 ABCBI C3435T genotypes. However, after renal transplantation, the peak plasma concentration (Cma ) and area under the plasma concentration-time curve (AUCO-24) of (R)-lansoprazole in patients with the ABCB1 C3435T C allele significantly increased, but not in patients with the TT genotype. These pharmacokinetic variations in (R)-lansoprazole did not influence the AUC of tacrolimus. There were no significant differences in the frequency of gastroesophageal symptoms among the three ABCB] C3435Tgenotypes. CONCLUSIONS: (R)-lansoprazole concentrations significantly increased in CYP2C19 extensive metabolizers with the ABCB1 C3435T C allele, but not TT genotype, after renal transplantation. However, the clinical relevance of this observation may be minor because these pharmacogenetic changes were not associated with the occurrence of gastroesophageal complications.
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2-Piridinilmetilsulfinilbencimidazoles/uso terapéutico , Hidrocarburo de Aril Hidroxilasas/genética , Reflujo Gastroesofágico/tratamiento farmacológico , Oxigenasas de Función Mixta/genética , Transportadores de Anión Orgánico/genética , Polimorfismo Genético , 2-Piridinilmetilsulfinilbencimidazoles/sangre , 2-Piridinilmetilsulfinilbencimidazoles/farmacocinética , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Administración Oral , Adulto , Alelos , Antiulcerosos/administración & dosificación , Antiulcerosos/farmacocinética , Antiulcerosos/uso terapéutico , Área Bajo la Curva , Hidrocarburo de Aril Hidroxilasas/metabolismo , Pueblo Asiatico/genética , Citocromo P-450 CYP2C19 , Dexlansoprazol , Femenino , Reflujo Gastroesofágico/etnología , Reflujo Gastroesofágico/genética , Genotipo , Semivida , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/farmacocinética , Inmunosupresores/uso terapéutico , Japón , Trasplante de Riñón , Lansoprazol , Masculino , Persona de Mediana Edad , Oxigenasas de Función Mixta/metabolismo , Tacrolimus/administración & dosificación , Tacrolimus/farmacocinética , Tacrolimus/uso terapéuticoRESUMEN
Excited states in (40)Si have been established by detecting gamma rays coincident with inelastic scattering and nucleon removal reactions on a liquid hydrogen target. The low excitation energy, 986(5) keV, of the 2(1)(+) state provides evidence of a weakening in the N=28 shell closure in a neutron-rich nucleus devoid of deformation-driving proton collectivity.
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This Letter reports on the (1)H((28)Ne, (28)Ne) and (1)H((28)Ne, (27)Ne) reactions studied at intermediate energy using a liquid hydrogen target. From the cross section populating the first 2(+) excited state of (28)Ne, and using the previously determined BE(2) value, the neutron quadrupole transition matrix element has been calculated to be M(n)=13.8 +/- 3.7 fm(2). In the neutron knockout reaction, two low-lying excited states were populated in (27)Ne. Only one of them can be interpreted by the sd shell model while the additional state may intrude from the fp shell. These experimental observations are consistent with the presence of fp shell configurations at low excitation energy in (27,28)Ne nuclei caused by a vanishing N=20 shell gap at Z=10.
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Síndrome de Behçet/patología , Encefalitis por Herpes Simple/diagnóstico , Encefalitis Viral/patología , Lóbulo Temporal/patología , Adulto , Síndrome de Behçet/fisiopatología , Encefalitis Viral/sangre , Encefalitis Viral/líquido cefalorraquídeo , Encefalitis Viral/fisiopatología , Enfermedades de los Genitales Masculinos/etiología , Enfermedades de los Genitales Masculinos/patología , Enfermedades de los Genitales Masculinos/virología , Antígenos HLA/metabolismo , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Lóbulo Temporal/virologíaRESUMEN
The biologic behavior of and optimal treatment for oral verrucous carcinoma (VC) remain controversial. We analyzed the clinicopathological characteristics of 12 patients with oral VC. Immunohistochemical techniques were used to evaluate p53 protein, CD44 variant 9, and proliferating cell nucleus antigen. The TNM classification (UICC, 1997) was T1 in 1 patient, T2 in 3, T3 in 4, and T4 in 4. All patients were classified as N0M0. Four patients were treated by surgery alone and 8 by surgery after chemotherapy, radiotherapy, or both. After surgery, two patients had primary recurrence of disease. Immunohistochemically, the proliferative activity of tumor cells as evaluated by proliferating cell nuclear antigen labeling index and p53 protein expression was similar in VC and well-differentiated squamous cell carcinoma. However, CD44 varient 9 expression was positive in 8 of 10 VC, suggesting that oral VC is associated with a low risk of lymph node metastasis. Positive CD44 variant 9 expression by most oral VCs, indicating a low risk of cervical lymph node metastasis, suggests that most cases can be controlled by surgical intervention.
Asunto(s)
Carcinoma Verrugoso/terapia , Neoplasias de la Boca/terapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Verrugoso/metabolismo , Carcinoma Verrugoso/cirugía , Terapia Combinada/métodos , Femenino , Humanos , Receptores de Hialuranos/análisis , Inmunohistoquímica/métodos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/cirugía , Antígeno Nuclear de Célula en Proliferación/análisis , Resultado del Tratamiento , Proteína p53 Supresora de Tumor/análisisRESUMEN
The electric quadrupole transition from the first 2(+) state to the ground 0(+) state in 16C is studied through measurement of the lifetime by a recoil shadow method applied to inelastically scattered radioactive 16C nuclei. The measured mean lifetime is 77+/-14(stat)+/-19(syst) ps. The central value of mean lifetime corresponds to a B(E2;2+(1)-->0(+)) value of 0.63e(2) fm(4), or 0.26 Weisskopf units. The transition strength is found to be anomalously small compared to the empirically predicted value.
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The present study was designed to investigate the incorporation of zinc (Zn) into cultured UMR-106 osteoblasts in response to mineralization caused by the addition of beta-glycerophosphate. As a result of the induced mineralization, the contents of calcium (Ca), phosphorus (P), and Zn in the monolayer increased, whereas the magnesium (Mg) content did not change. The activity of alkaline phosphatase (ALP) also increased during the process. The zinc distribution in the cell monolayer was studied using Zinquin, a fluorescent zinc ion chelator. The double fluorescent labeling with Zinquin and calcein revealed that zinc was localized both as intracellular vesicles and extracellular clusters, whereas calcium was colocalized with extracellular zinc. These results suggest that zinc is involved in the mineralization process of UMR-106 cells.
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Minerales/metabolismo , Osteoblastos/metabolismo , Zinc/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Calcio/metabolismo , Línea Celular , Quelantes/metabolismo , Fluoresceínas/metabolismo , Colorantes Fluorescentes/metabolismo , Glicerofosfatos/farmacología , Magnesio/metabolismo , Osteoblastos/efectos de los fármacos , Fósforo/metabolismo , Quinolonas/metabolismo , Ratas , Compuestos de Tosilo/metabolismoRESUMEN
Although zinc (Zn) is known to participate in bone formation, its exact role in the remodeling of this tissue has not been fully clarified. The present study was designed to investigate whether Zn has a role at the resorptive sites in vitro. We investigated the migration of osteoblastic MC3T3-E1 cells in response to Zn using a Boyden chamber assay. Exposure of MC3T3-E1 cells to Zn stimulated the migration of MC3T3-E1 cells. Checkerboard analysis revealed that the migration of MC3T3-E1 cells toward Zn was a directional (chemotaxis) rather than a random (chemokinesis) motion. Pretreatment of MC3T3-E1 cells with pertussis toxin completely blocked the chemotactic response of cells to Zn, indicating that it is mediated by G-protein-coupled receptors. Because the bone is one of the major Zn storage sites, we suggest that Zn released from bone-resorptive sites plays an important role in the recruitment of osteoblasts and bone renewal.