Takumi Takahashi

ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis.

Apoptosis signal‐regulating kinase (ASK) 1 is activated in response to various cytotoxic stresses including TNF, Fas and reactive oxygen species (ROS) such as H2O2, and activates c‐Jun NH2‐terminal kinase (JNK) and p38. However, the roles of JNK and p38 signaling pathways during apoptosis have been controversial. Here we show that by deleting ASK1 in mice, TNF‐ and H2O2‐induced sustained activations of JNK and p38 are lost in ASK1−/− embryonic fibroblasts, and that ASK1−/− cells are resistant to TNF‐ and H2O2‐induced apoptosis. TNF‐ but not Fas‐induced apoptosis requires ROS‐dependent activation of ASK1–JNK/p38 pathways. Thus, ASK1 is selectively required for TNF‐ and oxidative stress‐induced sustained activations of JNK/p38 and apoptosis.

ASK1-dependent recruitment and activation of macrophages induce hair growth in skin wounds.

Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein 3-kinase family that activates both c-Jun NH2-terminal kinase and p38 pathways in response to inflammatory cytokines and physicochemical stress. We report that ASK1 deficiency in mice results in dramatic retardation of wounding-induced hair regrowth in skin. Oligonucleotide microarray analysis revealed that expression of several chemotactic and activating factors for macrophages, as well as several macrophage-specific marker genes, was reduced in the skin wound area of ASK1-deficient mice. Intracutaneous transplantation of cytokine-activated bone marrow-derived macrophages strongly induced hair growth in both wild-type and ASK1-deficient mice. These findings indicate that ASK1 is required for wounding-induced infiltration and activation of macrophages, which play central roles in inflammation-dependent hair regrowth in skin.

Acceleration of Palatal Wound Healing in Smad3-deficient Mice

Wound healing is a well-orchestrated complex process leading to the repair of injured tissues. It is suggested that transforming growth factor (TGF)-β/Smad3 signaling is involved in wound healing. The purpose of this study was to investigate the role of TGF-β/Smad3 signaling in palatal wound healing in Smad3-deficient (Smad3−/−) mice. Histological examination showed that wound closure was accelerated by the proliferation of epithelium and dermal cells in Smad3−/− mice compared with wild-type (WT) mice. Macrophage/monocyte infiltration at wounded regions in Smad3−/− mice was decreased in parallel with the diminished production of TGF-β1, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1α compared with WT mice. Fibrocytes, expressing hematopoietic surface marker and fibroblast products, were recruited and produced α-smooth-muscle actin in WT mice, but were not observed in Smad3−/− mice. These results suggest that TGF-β/Smad3 signaling may play an important role in the regulation of palatal wound healing.

Efficient usage of implant anchorage to treat overerupted maxillary first molar and mesially inclined mandibular molars

This case report demonstrates the efficient use of implant anchorage in a patient with mesially inclined mandibular molars and an overerupted maxillary molar. A 14-year-old girl had an overerupted maxillary right first molar, possibly because of severely inclined mandibular right molars. Two-step use of miniplate anchorage in the right zygomatic process was proposed. As the first step, the overerupted maxillary first molar was intruded with elastic chains from the miniplate for 10 months. Then the maxillary right molars were distalized by using the miniplate to correct the Class II molar relationship. In the mandible, the first molar was extruded with intermaxillary elastics applied from the miniplate to the molar for 7 months after the uprighting of the mandibular right second molar. The results suggest that the use of 2-step implant anchorage is efficient for intrusion and distalization of maxillary molars and extrusion and uprighting of mandibular inclined molars.

Longitudinal Evaluation of Secondary Bone Grafting Into the Alveolar Cleft

Objective To longitudinally evaluate the outcome of secondary bone grafting (SBG) using computed tomograms (CTs) and conventional dental radiographs. Subjects Nineteen alveolar clefts from 17 patients were used in this study. Method A two-dimensional evaluation of SBG was performed using dental radiographs at 1 year after SBG by assigning scores of 1 to 4 (from very good to poor) based on postoperative marginal bone level on the alveolar side. On the basis of postoperative marginal bone levels on the nasal side, clefts were also assigned to groups with the bony bridge on or above (group I) or below (group II) a horizontal reference line. Three-dimensional evaluation of the SBG was performed on horizontal CT slices with the residual cortical bone (RCB) ratio before SBG (T0) as well as 1.5 (T1), 3 (T2), 6 (T3), and 12 months (T4) after SBG. Results The RCB ratio at T4 in the group with scores 1 and 2 was significantly smaller than that of score 3. Furthermore, the mean RCB ratio at T4 in group I was significantly smaller than that in group II. Nineteen alveolar clefts were divided into two groups, A and B, based on a cluster analysis of the RCB ratios. Group A showed a continuous decrease in the RCB ratio from T0 to T2, but group B showed a significant decrease only in the period from T0 to T1. Conclusion These results suggested that the RCB ratio might be a useful parameter for evaluation of the bony bridge after SBG.

Orthodontic occlusal reconstruction after conservative treatment of unicystic ameloblastoma in an adolescent patient: 10-year follow-up

Conservative treatment of an ameloblastoma often requires an occlusal reconstruction. In this article, we report the successful interdisciplinary treatment of a 14-year-old girl with a unicystic ameloblastoma in the mandible. One year after the marsupialization, enucleation with bone curettage was performed with extraction of the impacted third molar, but the proximal second molar could be maintained. The conservative treatment required long-term use of an obturator, and it caused a total open bite. Additionally, the patient genetically had a Class II malocclusion with severe crowding. Consequently, orthodontic treatment was performed after 4 premolar extractions. There was no recurrence of the ameloblastoma 10 years after the enucleation.

Blood flow distribution of repaired lip in cleft lip patients.

OBJECTIVE To investigate the blood flow distribution in the repaired lip of cleft patients using a laser Doppler imager and to evaluate the difference in blood flow of the scar tissue between unilateral cleft lip patients with and without cleft palate. MATERIALS AND METHODS Twenty patients with either unilateral cleft lip only (CL group, n = 8) or cleft lip and palate (CLP group, n = 12) were used as subjects. The blood flow of the upper lip was two-dimensionally visualized by a color scale alongside the corresponding photo image of the tissue surface with laser Doppler imaging. The upper lip photo image was divided into five regions: scar, white lip on the cleft side, white lip on the noncleft side, red lip on the cleft side, and red lip on the noncleft side. The average flux score (AFS), which is proportional to blood flow, was analyzed in each region. RESULTS The AFS for the scar region was significantly (P < .05) lower than in the other four regions. The AFS for the red lip on the cleft side was not significantly different from that for the noncleft side. The white lip revealed a significantly (P < .05) higher score on the cleft side than on the noncleft side. The AFS ratio (AFS in the scar region/AFS in the white lip region) was significantly (P < .01) lower in the CLP group than in the CL group. CONCLUSIONS These results suggest that blood flow distribution in the repaired lip might be affected by the anatomic features of the cleft.