Niigata University Medical and Dental Hospital
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ヒトI型コラーゲン由来ペプチドの骨再生能に及ぼす影響の解析と生体内での各種コラーゲン材との比較
Get PDF新潟大学Niigata University博士（医学）Background and Objectives: Autologous bone grafting is the first choice for reconstructive surgery in bone defects due to trauma or malignant tumors. However, there is an increasing demand for minimally invasive alternatives involving bone regeneration using artificial materials. Biomimetic materials that replicate the body’s microscopic structure, such as Cellnest®, are gaining attention. Cellnest is a xeno-free recombinant peptide based on human type I collagen, containing a rich Arg-Gly-Asp (RGD) motif related to cell adhesion. The aim of this study was to compare the effects of Cellnest with existing collagen materials (Pelnac®, Integra®, Terudermis®) on bone regeneration and elucidate the underlying mechanisms. Materials and Methods: In vivo experiments involved a rat model of calvarial bone defects, in which Cellnest and other collagen materials were implanted into the defect area. Bone formation was assessed after 4 weeks using micro-computed tomography (micro-CT) and histological analysis. In vitro experiments included the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), adhesion, and migration assays, and a real-time polymerase chain reaction using rapidly expanding cells (RECs) to explore the mechanisms of Cellnest’s bone regenerative capacity. Results: The micro-CT analysis showed that the regenerated bone area was significantly greater in the Cellnest group (72.3%) than in the Pelnac® (25.5%), Integra® (31.6%), and Terudermis® (38.3%) groups. The histological analysis confirmed similar trends, with Cellnest showing 42.2% bone regeneration, outperforming the other materials. The in vitro assays revealed that Cellnest promoted cell proliferation, adhesion, and migration. Gene expression analysis demonstrated that Cellnest significantly increased the levels of the bone formation markers ALP and COL1. Conclusions: Cellnest, a human type I collagen-like peptide rich in RGD motifs, enhances bone regeneration by promoting MSC adhesion and migration, and bone formation-related gene expression. The findings suggest its potential as an effective material for bone defect reconstruction.Asakura, T.; Diep, T.T.T.; Ueda, Y.; Yamada, A.; Tsuzuno, T.; Takahashi, N.; Miyata, M.; Tabeta, K.; Nagata, M.; Matsuda, K. Analysis of the Effect of Human Type I Collagen-Derived Peptide on Bone Regenerative Capacity and Comparison with Various Collagen Materials In Vivo. Medicina 2025, 61, 57. https://doi.org/10.3390/medicina61010057新大院博(医)第1253
MAP4K抑制の神経突起伸長への影響
No full text新潟大学博士（医学）Protein kinases are responsible for protein phosphorylation and are involved in important intracellular signal transduction pathways in various cells, including neurons; however, a considerable number of poorly characterized kinases may be involved in neuronal development. Here, we considered mitogen-activated protein kinase kinase kinase kinases (MAP4Ks), related to as candidate regulators of neurite outgrowth and synaptogenesis, by examining the effects of a selective MAP4K inhibitor PF06260933. PF06260933 treatments of the cultured neurons reduced neurite lengths, not the number of synapses, and phosphorylation of GAP43 and JNK, relative to the control. These results suggest that MAP4Ks are physiologically involved in normal neuronal development and that the resultant impaired neurite outgrowth by diminished MAP4Ks’ activity, is related to psychiatric disorders.Lasham, D.J., Arta, R.K., Hadi, A.F. et al. Effects of MAP4K inhibition on neurite outgrowth. Mol Brain 16, 79 (2023). https://doi.org/10.1186/s13041-023-01066-2新大院博（医）第1276
NF-κB RelA は、生後脳におけるオリゴデンドロサイト分化のタイミングを制御する
Get PDF新潟大学博士（医学）The NF-κB signaling pathway responds to a diverse range of cytokines and extracellular stresses, regulating immune responses, inflammation, cell proliferation, and cell death. However, the requirement of NF-κB in oligodendrocyte development and differentiation remains debatable. In this study, we generated conditional knockout mice of the RelA gene in the oligodendrocyte-lineage cells, which encodes a major subunit of NF-κB, and assessed its impact on oligodendrocyte differentiation. In RelA cKO mice, we observed a transient delay of oligodendrocyte differentiation in the postnatal cerebral cortex, albeit in a spatially and temporally restricted manner. Similarly, in the primary cultured oligodendrocyte differentiation model, the loss of RelA resulted in impaired terminal differentiation. Transcriptome analysis revealed a significant downregulation of numerous oligodendrocyte-related genes, including predicted NF-κB target genes. Furthermore, a comprehensive splicing analysis identified aberrant alternative splicing of Plp1, a most abundant and key gene involved in myelin sheath formation. These findings suggest that NF-κB/RelA contributes to the temporal and special control of oligodendrocyte development and differentiation in the postnatal brains. Our results highlight a previously underappreciated role of NF-κB in oligodendrocyte biology and encourage a re-evaluation of its physiological significance in the glial lineage.Sompub K, Bizen N, Baldwin AS and Takebayashi H (2025) NF-κB RelA regulates temporal oligodendrocyte differentiation in the postnatal brains. Front. Cell. Neurosci. 19:1622874. doi: 10.3389/fncel.2025.1622874新大院博（医）第1277
高齢心不全患者における虚弱および障害の有無による、多剤併用、ガイドラインに基づく薬物療法、および潜在的不適切な薬剤を含む薬剤プロファイルと全死亡率との関連
Get PDF新潟大学博士（医学）新大院博（医）第1279
