Effects of combined application of fibroblast growth factor (FGF)-2 and carbonate apatite for tissue regeneration in a beagle dog model of one-wall periodontal defect

Introduction: There has been an increasing desire for the development of predictive periodontal regenerative therapy for severe periodontitis. In this study, we investigated the effect of the combined use of fibroblast growth factor-2 (FGF-2), a drug for periodontal regeneration approved in Japan, and carbonated apatite (CO3Ap), bioresorbable and osteoconductive scaffold, on periodontal regeneration in beagle dog model of one-wall periodontal defect (severe intraosseous defect) for 24 weeks in comparison with CO3Ap or vehicle alone. Methods: One-wall periodontal defects were created (mesiodistal width × depth: 4 × 4 mm) on the mesial portion of the mandibular first molar (M1) of beagle dogs on both side. Mixture of FGF-2 and CO3Ap, vehicle and CO3Ap, or vehicle alone were administered to the defects and designated as groups FGF-2+CO3Ap, CO3Ap, and control, respectively. To assess the periodontal regeneration, radiographic analysis over time for 24 weeks, and micro computed tomography (μCT) and histological evaluation at 6 and 24 weeks were performed. Results: For the regenerated tissue in the defect site, the mineral content of the FGF-2+CO3Ap group was higher than that of the CO3Ap group in the radiographic analysis at 6–24 weeks. In the context of new bone formation and replacement, the FGF-2+CO3Ap group exhibited significantly greater new bone volume and smaller CO3Ap volume than the CO3Ap group in the μCT analysis at 6 and 24 weeks. Furthermore, the density of the new bone in the FGF-2+CO3Ap group at 24 weeks was similar to those in the control and CO3Ap groups. Histological evaluation revealed that the length of the new periodontal ligament and cementum in the FGF-2+CO3Ap group was greater than that in the CO3Ap group at 6 weeks. We also examined the effect of the combined use of the FGF-2 and CO3Ap on the existing bone adjacent to the defect and demonstrated that the existing bone height and volume in the FGF-2+CO3Ap group remained significantly greater than those in the CO3Ap group. Conclusion: This study demonstrated that the combination of FGF-2 and CO3Ap was effective not only in enhancing new bone formation and replacing scaffold but also in maintaining the existing bone adjacent to the defect site in a beagle dog model of one-wall periodontal defect. Additionally, new periodontal tissues induced by FGF-2 and CO3Ap may follow a maturation process similar to that formed by spontaneous healing. This suggests that the combined use of FGF-2 and CO3Ap would promote periodontal regeneration in severe bony defects of periodontitis patient

Inter-strain variation of apoptotic index of jejunal crypts between mouse systems after gamma ray whole body irradiation

In the clinic, interindividual differences in normal tissue response to radiotherapy have been observed and genetic factors are suggested to be responsible for this variation. Murine models have proven to be useful for the study of cytotoxic agents including radiation on the jejunum. We here report three murine strain differences in the levels of radiation-induced apoptosis in jejunal crypt cells. The apotosis positivity cell in jejunum carried out apoptosis index comparatively, and radiation susceptibility of strains was evaluated. Apoptosis index in C3 H/Hem was consistently lower than in A/J, or C57BL/6J at various times up to 24 hr after irradiation with 0.5 Gy. (P< 0.05). There was no difference among three strains after irradiation with 5 Gy. In the frequency of appearance of an apoptosis cell, C57BL/6J and A/J were radiation quantity susceptibility as compared with C3 H/Hem.日本放射線影響学会第４６回大

Inter-strain variation of skin reaction among three strains of mice after fractionated irradiation.

[Purpose]To clarify the mechanism the heterogeneity in the response to ionizing irradiation arising from a genetic variation between individual humans, we here investigated the irradiated skin reaction of mice fractionated irradiation with comparison of the results after single dose irradiation setting.[Material and Method]Female mice, 12 weeks old of the inbred strains C3H/HeMs, C57BL/6J, A/J were used through experiments. After Cs-137 gamma rays irradiated 10 fraction- 3, 4, 5, 6 Gy/ 12 days on right-hind legs, and comparison of fractionated irradiation with single dose. [Results]1. Radiosensitivity of a group of fractionated radiation was C3H/HeMs< A/J< C57BL/6J. 2. Latent periods appeared the same point in a group of single dose, but a group of fractionated radiation was different among three strains or irradiated dose. 3. Peak skin reaction score was exhibited dose dependency, although fractionated irradiation groups was low compared with single dose groups, the strain difference was not observed in each irradiation group. But low dose was not displayed dose dependency, the strain difference observed.[Discussion] Inter-strain differences were observed in radiation susceptibility among three strains of mice using the functional endpoint of skin reaction after local fractionated irradiation. In particular, peak skin reaction score in latent periods and low dose observed strain difference.日本放射線影響学会第４６回大