Morphogenesis of the heart requires development of the endocardial cushion tissue that gives rise to the membranous septa and valves. Here we show that Meltrin beta/ADAM19, a novel metalloprotease-disintegrin, participates in the development of the endocardial cushion. Mice lacking Meltrin beta exhibit ventricular septal defect (VSD) and immature valves, and most of the animals die soon after birth. During development of the endocardial cushion, epithelial-mesenchymal transformation (EMT) of endocardial epithelial cells generates most of the cushion mesenchymes that constitute the main components of the septa and valves. Meltrin beta is expressed in both the epithelia and the mesenchymes of the endocardial cushion. In the absence of Meltrin beta, the cushion is small or thin in the septum-forming region and show poor remodeling of cardiac jelly components; both of these characteristics suggest impaired growth and differentiation of the endocardial cushion. When embryonic fibroblasts are cultured sparsely, Meltrin beta-lacking cells exhibit aberrant ectodomain shedding of type I Neuregulin, one of the ErbB ligands expressed in endocardial cells. These results suggest the necessity of proteolytic regulation of ErbB ligands by Meltrin beta for proper heart development.
Background/Aim: Due to its abilities of substance adsorption and intracellular transportation, hydroxyapatite is a potential carrier in drug delivery systems (DDS). This in vitro study investigated whether newly-developed, highlydispersive calcined hydroxyapatite nanoparticles with an average grain diameter of 20 nm (nano-SHAP) were suitable as a DDS for the drugs zoledronic acid (ZA), cisplatin, and carboplatin. Material and Methods: The effects of drugbearing nano-SHAP on cell proliferation were assessed using three human oral squamous cell carcinoma cell lines (HSC-4, KOSC, and SAS) and one human breast cancer cell line (MCF-7). Results: Nano-SHAP alone did not affect proliferation of any cell line until a concentration of 1 μg/ml was reached. Although the effective concentration of ZA in ZA-bearing nano-SHAP differed, it inhibited cell proliferation better than ZA alone. Cisplatin and carboplatin-bearing nano-SHAP had the same effect as these drugs alone. Conclusion: The nano-SHAP system is of potential use as a drug delivery system. Hydroxyapatite (HAP), which has a structural formula of Ca 10 (PO 4 ) 6 (OH) 2 , is the principal inorganic constituent of human bones and teeth (1, 2). HAP is widely used in medical applications, including treating bone defects, tissue engineering systems, and bioactive coatings on metallic osseous implants (1-3). Hydroxyapatite nanoparticle (nano-HAP) structures have a large surface area, high loading capacity, and are capable of intracellular transportation. As a result, nano-HAP has been explored as a therapeutic molecule for drug delivery systems (DDS) (2, 3). Since nano-HAP has 6715
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