神経誘導因子Netrin-1は軟骨形成や骨形成においてBMPまたはNogginにより調節される

This is the first report describing neurogenic factor of Netrin-1 related to chondrogenesis or osteogenesis in a human cells. Netrin is a morphogenetic factor that induces a growth cone of an axial filament of the nervous system. However, the roles of Netrin in chondrogenesis or osteogenesis are not yet understood. We analyzed the relationship between Netrin and bone morphogenetic protein-2 (BMP-2) in chondrogenesis or osteogenesis, using a human chondrocyte-like cell line (USAC), which also retains multi-potency to differentiate into osteoblasts and adipocytes. Netrin-1 mRNA was decreased in USAC cells, though the expression was increased during osteogenic differentiation at the stage when osteocalcin mRNA were increased by BMP-2. Furthermore, inhibition of Netrin-1 gene increased Cbfa1 mRNA expression, and decreased Sox9 mRNA expression. We also found that Netrin-1was strongly expressed in immature chondrocytes of cartilage-like tissues that were formed in an exo vivo experiment with diffusion chambers. The se findings indicate that Netrin-1 and BMP-2 regulates in the stage dependent process of mesenchymal cell differentiation to chondrocytes or osteoblasts.骨芽細胞または脂肪細胞への分化多能を保持するヒト軟骨細胞様細胞系(USAC)を用い、軟骨形成または骨形成におけるNetrinと骨形成蛋白質-2(BMP-2)との関係を調べた。Netrin-1 mRNAはUSAC細胞中では減少するが、オステオカルシンmRNA濃度がBMPによって上昇する際の骨芽細胞分化時にNetrin-1 mRNAの発現が増加した。Netrin-1遺伝子を阻害すると、Cbfal mRNA発現は増加しSox9 mRNA発現は減少した。またNetrin-1は軟骨様組織の未成熟軟骨細胞において強く発現した。Netrin-1とBMP-2が、間葉細胞の軟骨細胞または骨芽細胞へ分化プロセスを制御すると考えた

日本人成人におけるパノラマX線写真上の下顎皮質骨と海綿骨構造との関係：コーンビームCTによる分析

Objectives The purpose of this study was to assess the association between the cortical shape of the mandible, as detected on panoramic radiographs, and trabecular bone structure, as assessed by cone-beam computed tomography (CBCT), in Japanese adults. Methods Panoramic radiographs and CBCT images of the mandibles of 50 subjects (18 men, 32 women), aged 45–86 years, were evaluated. An experienced oral and maxillofacial radiologist categorized the cortical shape of the mandible as detected on panoramic radiographs as normal, mildly to moderately eroded, and severely eroded cortices, respectively. All mandibles were scanned using CBCT. Four bone structure parameters of the basal portion of the mandible were calculated in three dimensions using an image-analysis system: total bone volume (mm3); cortical bone volume fraction (%); trabecular bone volume fraction (%); fractal dimension. One-way analysis of covariance with Bonferroni correction was employed to evaluate differences in the four bone parameters among the three cortical shape groups. Pearson’s correlation coefficient was calculated to examine correlations between age and cortical and trabecular bone volume fractions.Results Progression of cortical bone erosion was significantly associated with increased trabecular bone volume fraction (P\0.001) and increased fractal dimension(P = 0.01). Cortical bone volume fraction decreased significantly with age (P = 0.04). However, trabecular bone volume fraction tended to increase with age (P = 0.06). Conclusions The change in the trabecular bone structure of the mandible may differ from that of the general skeleton in Japanese adults.2013博士（歯学）松本歯科大

Wortmannin, a specific inhibitor of phosphatidylinositol-3 kinase, blocks osteoclastic bone resorption

AbstractThe biological role of phosphatidylinositol (PI)-3 kinase was examined in osteoclast-like multinucleated cells (OCLs) formed in co-cultures of mouse osteoblastic cells and bone marrow cells. The expression of PI-3 kinase in OCLs was confirmed by Western blot analysis. Wortmannin (WT), a specific inhibitor of PI-3 kinase, inhibited PI-3 kinase activity in OCLs both in vitro and in vivo. WT also inhibited pit-forming activity on dentine slices and disrupted a ringed structure of F-actin-containing dots (an actin ring) in OCLs in a dose-dependent manner. The inhibitory profiles of WT for pit and actin ring formation were similar to that for PI-3 kinase activity in OCLs. Electron microscopic analysis revealed that OCLs treated with WT did not form ruffled borders. Instead, numerous electron lucent vacuoles of differing sizes were found throughout the cytoplasm. These results suggest that PI-3 kinase is important in osteoclastic bone resorption

Regulation of bone metabolism by vitamin D

ビタミンD欠乏はくる病・骨軟化症を発症する。さまざまな遺伝子改変動物の解析は、小腸におけるカルシウム(Ca)吸収の抑制がくる病・骨軟化症の発症にかかわることを示す。一方、1α(OH)D3やエルデカルシトールの薬理量を長期間投与すると、骨吸収抑制を伴う骨量増加作用を示す。この骨作用において、活性型ビタミンDが破骨細胞・破骨細胞前駆細胞に作用し骨吸収を抑制する可能性と、骨芽細胞に作用し破骨細胞形成支持環境を抑制する可能性が指摘される