Damage-induced neuronal endopeptidase (DINE)/endothelin-converting enzyme-like 1 (ECEL1) is a membrane-bound metalloprotease that we identified as a nerve regeneration-associated molecule. The expression of DINE is upregulated in response to nerve injury in both the peripheral and central nervous systems, while its transcription is regulated by the activating transcription factor 3 (ATF3), a potent hub-transcription factor for nerve regeneration. Despite its unique hallmark of injury-induced upregulation, the physiological relevance of DINE in injured neurons has been unclear. In this study, we have demonstrated that the expression of DINE is upregulated in injured retinal ganglion cells (RGCs) in a coordinated manner with that of ATF3 after optic nerve injury, whereas DINE and ATF3 are not observed in any normal retinal cells. Recently, we have generated a mature DINE-deficient (KOTg) mouse, in which exogenous DINE is overexpressed specifically in embryonic motor neurons to avoid aberrant arborization of motor nerves and lethality after birth that occurs in the conventional DINE KO mouse. The DINE KOTg mice did not show any difference in retinal structure and the projection to brain from that of wild–type (wild type) mice under normal conditions. However, injured RGCs of DINE KOTg mice failed to regenerate even after the zymosan treatment, which is a well-known regeneration-promoting reagent. Furthermore, a DINE KOTg mouse crossed with a Atf3:BAC Tg mouse, in which green fluorescent protein (GFP) is visualized specifically in injured RGCs and optic nerves, has verified that DINE deficiency leads to regeneration failure. These findings suggest that injury-induced DINE is a crucial endopeptidase for injured RGCs to promote axonal regeneration after optic nerve injury. Thus, a DINE-mediated proteolytic mechanism would provide us with a new therapeutic strategy for nerve regeneration.

The aim of this in vivo study was to evaluate the utility of bone graft gel containing hydroxyapatite nanoparticles in promoting bone regeneration in a mouse model of vertical bone augmentation. Materials and Methods: Gel implants with high and low viscosity were compared for their bone regenerating ability. Bone formation at 12 weeks and material reactions were observed radiographically and histologically. Results: Radiological analysis showed that most bone augmentation area in the graft material occurred in the fourth week after surgery regardless of the viscosity of the gel, and then gradually decreased. The volume of bone augmentation area was greater in the high-viscosity implant group than in the lowviscosity implant group at all time points, the difference was statistically significant at 8 and 12 weeks. Histological evaluation indicated that the new bone area was significantly smaller in the high-viscosity implant group. Conclusion: Gelatinous graft materials containing hydroxyapatite nanoparticles were confirmed to be useful in vertical bone augmentation.Graft materials used for formation of bone tissue in dentistry include autologous bone, allogeneic bone, xenograft tissue, and artificial bone (1-5). Although many approved bone substitute materials are granular, problems remain concerning operability and dissemination to surrounding tissues. There are several clinical reports on the use of granular 1053 This article is freely accessible online.

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