Cyclophosphamide Promotes Arrested Development of the Dental Root in Mice

Cyclophosphamide (CPA) is a commonly used chemotherapeutic agent to treat cancer. Among its many side effects is the well-known consequence on tooth development when administered at early ages. This study elucidated the effects of CPA on development of the mandibular molar in mice. Mice received a single intraperitoneal injection of CPA at different doses and development times. CPA treatment led to weight loss and alopecia but had no effect on disturbances in tooth eruption or crown shape. However, at higher doses, there was arrested root development and early apical foramen closure histologically related to the formation of the cervical loop structure in the apical portion of the root. In cell culture experiments, the Hertwig\u27s epithelial root sheath cell line (HERS01a) was cultured with or without CPA. At high doses of CPA, HERS01a cells showed decreases in E-cadherin expression, while N-cadherin expression was upregulated, indicating that this cadherin switch may promote an epithelial-to-mesenchymal transition (EMT)-like phenomenon. These findings suggest that administration of high doses of CPA can lead to arrested root development of the molars and an EMT-like phenomenon.福岡歯科大学2019年

Transforming growth factor-beta and sonic hedgehog signaling in palatal epithelium regulate tenascin-C expression in palatal mesenchyme during soft palate development.

福岡歯科大学2020年

Cisplatin-Induced Sonic Hedgehog Signaling Mediates Epithelial-Mesenchymal Transition in Hertwig’s Epithelial Root Sheath Cells.

福岡歯科大学2020年

Use of the index of pulmonary vascular disease for predicting long-term outcome of pulmonary arterial hypertension associated with congenital heart disease

AimsLimited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categories based on severity: (1) no intimal thickening, (2) cellular thickening of the intima, (3) fibrous thickening of the intima, and (4) destruction of the tunica media, with the overall grade expressed as an additive mean of these scores. This study aimed to investigate the relationship between IPVD and the long-term outcome of CHD-PAH.MethodsThis retrospective study examined lung pathology images of 764 patients with CHD-PAH aged <20 years whose lung specimens were submitted to the Japanese Research Institute of Pulmonary Vasculature for pulmonary pathological review between 2001 and 2020. Clinical information was collected retrospectively by each attending physician. The primary endpoint was cardiovascular death.ResultsThe 5-year, 10-year, 15-year, and 20-year cardiovascular death-free survival rates for all patients were 92.0%, 90.4%, 87.3%, and 86.1%, respectively. The group with an IPVD of ≥2.0 had significantly poorer survival than the group with an IPVD <2.0 (P = .037). The Cox proportional hazards model adjusted for the presence of congenital anomaly syndromes associated with pulmonary hypertension, and age at lung biopsy showed similar results (hazard ratio 4.46; 95% confidence interval: 1.45–13.73; P = .009).ConclusionsThe IPVD scoring system is useful for predicting the long-term outcome of CHD-PAH. For patients with an IPVD of ≥2.0, treatment strategies, including choosing palliative procedures such as pulmonary artery banding to restrict pulmonary blood flow and postponement of intracardiac repair, should be more carefully considered

Macrophage inflammatory protein–1α as a costimulatory signal for mast cell–mediated immediate hypersensitivity reactions

Regulation of the immune response requires the cooperation of multiple signals in the activation of effector cells. For example, T cells require signals emanating from both the TCR for antigen (upon recognition of MHC/antigenic peptide) and receptors for costimulatory molecules (e.g., CD80 and CD60) for full activation. Here we show that IgE-mediated reactions in the conjunctiva also require multiple signals. Immediate hypersensitivity reactions in the conjunctiva were inhibited in mice deficient in macrophage inflammatory protein–1α (MIP-1α) despite normal numbers of tissue mast cells and no decrease in the levels of allergen-specific IgE. Treatment of sensitized animals with neutralizing antibodies with specificity for MIP-1α also inhibited hypersensitivity in the conjunctiva. In both cases (MIP-1α deficiency and antibody treatment), the degranulation of mast cells in situ was affected. In vitro sensitization assays showed that MIP-1α is indeed required for optimal mast cell degranulation, along with cross-linking of the high-affinity IgE receptor, FcεRI. The data indicate that MIP-1α constitutes an important second signal for mast cell degranulation in the conjunctiva in vivo and consequently for acute-phase disease. Antagonizing the interaction of MIP-1α with its receptor CC chemokine receptor 1 (CCR1) or signal transduction from CCR1 may therefore prove to be effective as an antiinflammatory therapy on the ocular surface

Generation of a new mouse line with conditionally activated signaling through the BMP receptor, ACVR1: A tool to characterize pleiotropic roles of BMP functions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168351/1/dvg23419.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168351/2/dvg23419_am.pd

CO2 laser therapy accelerates the healing of ulcers in the oral mucosa by inducing the expressions of heat shock protein-70 and tenascin C

The treatment of ulceration or stomatitis with laser therapy is known to accelerate healing and relieve pain, but the underlying biological mechanism is not fully understood. The present study used a mouse model of ulceration to investigate the molecular mechanisms by which CO2 laser therapy accelerated the wound healing process. An ulcer was experimentally created in the palatal mucosa of the mouse and irradiated with light from a CO2 laser. Compared with controls (no irradiation), laser irradiation induced the proliferation of epithelial cells and faster re-epithelialization of the wound area. Immunohistochemistry experiments showed that heat shock protein-70 (HSP70) was expressed mainly in the epithelium of normal palatal tissue, whereas there was little tenascin C (TnC) expression in the epithelium and mesenchyme under normal conditions. Laser irradiation induced HSP70 mRNA and protein expression in the lamina propria as well as TnC expression in the mesenchyme underlying the renewing epithelium. Epithelial cells and fibroblasts were exposed to heated culture medium or laser irradiation to establish whether hyperthermia mimicked the effect of laser irradiation. Culture of fibroblasts in heated medium increased the expressions of both TnC and TGF-β1, whereas laser irradiation induced only TnC expression. The present study indicates that CO2 laser irradiation exerts a photobiogenic effect to up-regulate TnC expression without inducing TGF-β1 expression. We suggest that CO2 laser therapy has an advantage over thermal stimulation

Podoplanin is dispensable for mineralized tissue formation and maintenance in the Swiss outbred mouse background

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/170814/1/dvg23450.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/170814/2/dvg23450_am.pd