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Carboxypeptidase E (CPE) is a prohormone/proneuropeptide processing enzyme, and mice bearing CPE mutations exhibit an obese and diabetic phenotype. Studies on CPE knockout (KO) mice revealed poor prohormone processing, resulting in deficiencies in peptide hormones/neuropeptides such as insulin, gonadotropin-releasing hormone, and cocaine-and amphetamine-regulated transcript (CART). Here, we show that CPE KO mice, an obese animal model, have low bone mineral density (BMD) accompanied by elevated plasma CTX-1 (carboxy-terminal collagen crosslinks), and osteocalcin, indicators of increased bone turnover. Receptor activator for NF-[kappa]B ligand (RANKL) expression was elevated ~2-fold relative to osteoprotegerin in the femur of KO animals, suggesting increased osteoclastic activity in the KO mice. In the hypothalamus, mature CART, a peptide involved in eating behavior and implicated in bone metabolism, was undetectable. The melanocortin and neuropeptide Y (NPY) systems in the hypothalamus have also been implicated in bone remodeling, since MC4R KO and NPY KO mice have increased BMD. However, reduction of [alpha]-MSH, the primary ligand of MC4R by up to 94% and the lack of detectable NPY in the hypotbalamus of CPE KO do not recapitulate the single-gene KO phenotypes. This study highlights the complex physiological interplay between peptides involved in energy metabolism and bone formation and furthermore suggests the possibility that patients, bearing CPE and CART mutations leading to inactive forms of these molecules, may be at a higher risk of developing osteoporosis. doi: 10.1152/ajpendo.00516.2009.

Nerve guidance channels (NGCs) promote cell‐extracellular matrix (ECM) interactions occurring within the nanoscale. However, studies focusing on the effects of nanophase topography on neural cell functions are limited, and mostly concentrated on the sub‐micron level (>100 nm) surface topography. Therefore, the aim of this study was to fabricate <100 nm sized structures on poly lactic‐co‐glycolic acid (PLGA) films used in NGC applications to assess the effects of nanophase topography on neural cell functions. For this purpose, nanopit surface arrays were fabricated on PLGA surfaces via replica molding method. The results showed that neural cell proliferation increased up to 65% and c‐fos protein expression increased up to 76% on PLGA surfaces having nanophase surface arrays compared to the control samples. It was observed that neural cells spread to a greater extend and formed more neurite extensions on the nanoarrayed surfaces compared to the control samples. These results were correlated with increased hydrophilicity and roughness of the nanophase PLGA surfaces, and point toward the promise of using nanoarrayed surfaces in NGC applications. [ABSTRACT FROM AUTHOR]