Design and synthesis of gene-directed caged cyclic nucleotides exhibiting cell type selectivity

We designed a new caging group that can be photoactivated only in the presence of a non-endogenous enzyme when exposed to 405 nm light. Because cells or tissues can be genetically tagged by an exogenously expressed enzyme, this novel method can serve as a strategy for adding targeting abilities to photocaged compounds

Histochemical examination on principal collagen fibers in periodontal ligaments of ascorbic acid-deficient ODS-od/od rats

In this study, we aimed to clarify the role of ascorbic acid in collagen synthesis in periodontal ligaments using osteogenic disorder Shionogi (ODS)/ShiJcl-od/od rats lacking L-gulonolactone oxidase. These rats cannot synthesize ascorbic acid in vivo. Eight-week-old ODS/ShiJcl-od/od male rats were administered ascorbic acid solution at a concentration of 200 mg/dL (control group, n = 6) or ascorbic acid solution at concentration of 0.3 mg/dL (insufficient group, n = 12). Six rats of the insufficient group were then given with ascorbic acid solution at concentration of 200 mg/dL for additional 3 weeks (rescued group, n = 6), and then, their mandibles were histochemically examined. Consequently, the insufficient group specimens were seen to possess fewer collagen fibers, and silver impregnation revealed numerous fine, reticular fiber-like fibrils branching off from collagen in the periodontal ligaments. In control group, faint immunoreactivities for matrix metalloproteinase (MMP)2 and cathepsin H were seen in the periphery of blood vessels and throughout the ligament, respectively. In contrast, in the insufficient group, intense MMP2-immunoreactivity was observed to be associated with collagen fibrils in the periodontal ligaments, and cathepsin H-immunopositivity was seen in ligamentous cells. The rescued group showed abundant collagen fibers filling the periodontal ligament space. Under transmission electron microscopy, ligamentous fibroblasts incorporated collagen fibrils into tubular endosomes/lysosomes while simultaneously synthesizing collagen fibril bundles. Thus, ascorbic acid insufficiency affected the immunolocalization of cathepsin H and MMP2; however, ligamentous fibroblasts appear to possess the potential to synthesize collagen fibers when supplied with ascorbic acid

The diversity of preosteoblastic morphology : Preosteoblastic response to parathyroid hormone

The current concept of a preosteoblast is a precursor of an osteoblast, which is regarded as a transient cell type during osteoblastic differentiation. We have previously demonstrated different phenotypes of preosteoblasts expressing Runx2, ALPase, and BrdU incorporation. Transmission electron microscopy revealed following four distinct preosteoblastic cell types : 1) cells rich in rough endoplasmic reticulum (rER) but with a few vesicles and vacuoles (ERrich/vesicle-poor preosteoblasts), 2) cells extending their cytoplasmic processes connecting distant cells, with a small amount of scattered cisterns of rER and many vesicles and vacuoles (ER-poor/vesicle-rich preosteoblasts), 3) translucent cells showing few dispersed cell organelles and irregular cell shape with a translucent cytoplasm (translucent cells), and 4) small cells without developed cell organelles (small undifferentiated cells). ER-rich/vesicle-poor preosteoblasts were often closely adjacent to mature osteoblasts and therefore appeared to be ready for differentiation into osteoblasts. In contrast, after the administration of parathyroid hormone (PTH), ER-poor/vesicle-rich preosteoblasts rather than ER-rich/vesicle-poor cells significantly increased in number, forming a huge meshwork overlying mature osteoblasts. Thus, ERpoor/vesicle-rich preosteoblasts appeared to respond well to PTH. We also attempted to unveil the cellular behavior of these preosteoblasts against PTH and to dissect the role of osteoclasts on the mediation of PTH anabolic actions. PTH stimulated the proliferation of ER-poor/vesicle-rich preosteoblasts and bone formation in mature osteoblasts. However, an increased population of ER-poor/vesicle-rich preosteoblasts appears to require cell coupling from osteoclasts to differentiate into ER-rich/vesicle-poor preosteoblasts and mature osteoblasts. Without osteoclasts, PTH could induce neither preosteoblastic differentiation into mature osteoblasts nor subsequent bone formation. In this mini-review, we will introduce preosteoblasts in vivo consisting of several cell types with different ultrastructural properties and PTH action on preosteoblasts

Data from: Hypoperfusion of the adventitial vasa vasorum develops an abdominal aortic aneurysm

The aortic wall is perfused by the adventitial vasa vasorum (VV). Tissue hypoxia has previously been observed as a manifestation of enlarged abdominal aortic aneurysms (AAAs). We sought to determine whether hypoperfusion of the adventitial VV could develop AAAs. We created a novel animal model of adventitial VV hypoperfusion with a combination of a polyurethane catheter insertion and a suture ligation of the infrarenal abdominal aorta in rats. VV hypoperfusion caused tissue hypoxia and developed infrarenal AAA, which had similar morphological and pathological characteristics to human AAA. In human AAA tissue, the adventitial VV were stenotic in both small AAAs (30–49 mm in diameter) and in large AAAs (> 50 mm in diameter), with the sac tissue in these AAAs being ischemic and hypoxic. These results indicate that hypoperfusion of adventitial VV has critical effects on the development of infrarenal AAA

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Hypoperfusion of the Adventitial Vasa Vasorum Develops an Abdominal Aortic Aneurysm

<div><p>The aortic wall is perfused by the adventitial vasa vasorum (VV). Tissue hypoxia has previously been observed as a manifestation of enlarged abdominal aortic aneurysms (AAAs). We sought to determine whether hypoperfusion of the adventitial VV could develop AAAs. We created a novel animal model of adventitial VV hypoperfusion with a combination of a polyurethane catheter insertion and a suture ligation of the infrarenal abdominal aorta in rats. VV hypoperfusion caused tissue hypoxia and developed infrarenal AAA, which had similar morphological and pathological characteristics to human AAA. In human AAA tissue, the adventitial VV were stenotic in both small AAAs (30–49 mm in diameter) and in large AAAs (> 50 mm in diameter), with the sac tissue in these AAAs being ischemic and hypoxic. These results indicate that hypoperfusion of adventitial VV has critical effects on the development of infrarenal AAA.</p></div

Characterization of rats that underwent polyurethane catheter insertion and aortic ligation resulting in aortic aneurysms (group IV).

<p>Data were collected using aortic specimens harvested on postoperative day 28 (n = 10). Group I was used as a control group. The specimens included infra-renal proximal aorta (Prox.A) and aneurysmal sac (Sac). All data are expressed as means ± standard deviation. (<b>A</b>) Representative photomicrographs of smooth muscle cells (SMCs; alpha-smooth muscle cell actin, ASMA), elastin (Elastica van Gieson staining, EVG), and collagen fibers (picrosirius red; PSR). Scale bar in upper panels = 500 μm, in lower panels = 100 μm. (<b>B</b>) Quantitative analysis of SMC, elastin fragmentation and collagen distribution. SMC depletion was scored as mild (1) to severe (5) using a histological grading system. Areas positive for collagen fibers were quantitated per aortic section. Results are means ± standard deviation of three independent experiments. Statistical analysis was performed using analysis of variance for comparisons among the three groups. Post-hoc comparison was performed using Tukey’s test. **P<0.01 indicates a statistically significant difference.</p