Tissue engineering and bone regeneration techniques using mesenchymal stem cells (MSCs) have started to be applied to the field of oral and maxillofacial surgery. Clinically, a shortened treatment time and improved efficiency are necessary because of the patients' needs and the running cost of cell culture. In the present study, the cultivation process for human MSCs (hMSCs) was examined by regulating the Wnt signaling pathway. We activated Wnt signaling with LiCl and inhibited Wnt signaling with sFRP-3 (secreted Frizzled-Related Protein-3). The proliferation of LiCl-treated hMSCs was examined by studying the cell growth rate and performing BrdU assays. Osteogenic differentiation of sFRP-3-treated hMSCs was examined by alizarin red staining, and osteogenic gene expression on days 7 and 14 after induction was examined by reverse-transcription polymerase chain reaction (RT-PCR) analysis and quantitative real-time RT-PCR analysis. LiCl-treated hMSCs showed increased cell numbers and BrdU-positive cells as compared to the untreated cells. Alizarin red staining showed early mineralization of hMSCs on day 7 of the sFRP-3 treatment. A high expression level of the alkaline phosphatase gene on days 7 and 14 of sFRP-3 treatment was also demonstrated. These results suggest that the regulation of the Wnt signaling pathway contributes to the increased cell numbers and the early osteogenic differentiation of hMSCs. This study supports the possibility that the regulation of the Wnt signaling pathway contributes to the development of effective and efficient bone regeneration techniques.
Branching morphogenesis of the fetal mouse submandibular gland (SMG) is regulated by signaling through the ErbB and FGF families of tyrosine kinase receptors, whose members activate the ERK-1/2 pathway. The four Sprouty (Spry) proteins are inhibitory modulators of ERK-1/2. There is little information on their expression during pre- and postnatal development of the SMG. Qualitative RT-PCR detected mRNAs for Spry1, 2, and 4 from embryonic day 13 (E13) through postnatal day 7 (P7), but only trace amounts of Spry1 and 2 in adult SMGs. More sensitive quantitative RT-PCR revealed that transcripts for all four Spry isoforms are expressed, and each shows individual patterns of variation across fetal and early postnatal stages, and that there are very low levels of Spry1 and 2, but no Spry3 and 4, in adult glands. EGF, FGF7 and FGF10 upregulate expression of mRNA for Spry1, but only FGF7 upregulates Spry2 mRNA. EGF strongly induces an activating phosphorylation of all four Spry isoforms, but both FGFs do so only minimally. Quantitative RT-PCR of samples collected by laser capture microdissection showed that transcripts for Spry1 are confined to the epithelium of E13 SMG rudiments. The isoform-specific temporal variation in the patterns of expression of Spry1, 2, 3 and 4 suggests a potentially important role for these negative modulators of growth-factor driven ras/ERK-1/2 signaling at stages when the SMG is most actively undergoing branching morphogenesis.
The patch test is the most reliable method for diagnosing a metal allergy. However, interpretation of patch test results depends on the experience of the investigator and on the conditions of the individual patient. In the case of patch tests for metal salts, irritant reactions such as pustular or follicular reactions are quite common. Therefore, one must be careful not to interpret irritant reactions as allergic responses, and objective standards to evaluate erythema in patch tests need to be established. In the present study, we attempted to objectively evaluate patch test results for metal salts using an erythema index meter. We used the Erythema Index Difference (EID) (patch test site erythema index (EI) minus the mean EI of healthy skin outside the patch test area and at the unit tape site) rather than the EI itself in order to eliminate the effects of the patch test unit and individual differences. We measured the EID over time in patients with suspected metal allergies to various metals. Significant differences in EID were observed among ++ assessments, + assessments and irritant reactions based on International Contact Dermatitis Research Group (ICDRG) standards. In considering changes in EID over time, allergic and irritant reactions can be discriminated with high sensitivity (73.3%) and specificity (91.2%). These results suggest that the measurement of erythema over time with an erythema index meter is useful for the objective assessment of metal patch test reactions.
To elucidate the histological findings of the anlage of the mandibular condyle during very early developmental stages, we analyzed sagittal and frontal plane serial sections of mouse fetuses for which the gestational period was precisely determined. An aggregate of mesenchymal cells around the buccal nerve (peripheral cell aggregate) could be seen at 12.0 days post-conception (dpc). Another cell aggregate (core cell aggregate), which almost coincided with the outline of the condylar head, was detected on the inside of the dome-shaped peripheral cell aggregate at 12.75 dpc. The cells of the peripheral cell aggregate were gradually flattened in accordance with cell differentiation, and formed a fibrous sheath covering the condylar head by 15.0 dpc. The cells of the central region of the core cell aggregate differentiated into hypertrophic chondrocytes by 14.5 dpc, whereas the cells of the fringe of the core cell aggregate differentiated into osteogenic cells to form the bone collar by 15.0 dpc. The continuity of the anlage of the condyle with that of the mandibular ramus was first recognized at 13.0 dpc. As the anlage of the mandibular condyle was observed histologically during very early developmental stages, further research is necessary to characterize the development of this anlage in greater detail.
Cat cry syndrome (cri-du-chat syndrome) is an extremely rare condition characterized by a high shrill cry during infancy, resulting from either the deletion of the short arm of chromosome 5 or unbalanced translocation inherited from a parent. We report the case of a 1-year-old girl with cat cry syndrome associated with cleft lip. The patient showed a ventricular septal defect, cleft lip, growth and mental retardation, micrognathia, ptosis of the eyelids, hypertelorism, epicanthal folds, and a preauricular tag on the right side. A chromosomal study revealed the terminal deletion of chromosome 5 (46, XX, del(p14.2)ish del(5)). Repair of the cleft lip was carried out concurrently with resection of the preauricular tag, and the patient's postoperative course was uneventful.
Schwannoma is a benign neoplasm originating from the neural sheath and occurs most commonly in the soft tissues of the head and neck. Intraosseous schwannoma in the maxillofacial region is extremely rare. The present study reports the case of an intraosseous schwannoma located in the mandibular symphysis of a 27-year-old male patient. The tumor was completely excised, and there has been no evidence of recurrence in the nearly two years since the operation. A review of the related literature is also included.