-AMP-activated protein kinase (AMPK) is a meta-bolic stress sensor present in all eukaryotes. A dominant missense mutation (R225Q) in pig PRKAG3, encoding the muscle-specific ␥3 isoform, causes a marked increase in glycogen content. To determine the functional role of the AMPK ␥3 isoform, we generated transgenic mice with skeletal muscle-specific expression of wild type or mutant (225Q) mouse ␥3 as well as Prkag3 knockout mice. Glycogen resynthesis after exercise was impaired in AMPK ␥3 knock-out mice and markedly enhanced in transgenic mutant mice. An AMPK activator failed to increase skeletal muscle glucose uptake in AMPK ␥3 knock-out mice, whereas contraction effects were preserved. When placed on a high fat diet, transgenic mutant mice but not knock-out mice were protected against excessive triglyceride accumulation and insulin resistance in skeletal muscle. Transfection experiments reveal the R225Q mutation is associated with higher basal AMPK activity and diminished AMP dependence. Our results validate the muscle-specific AMPK ␥3 isoform as a therapeutic target for prevention and treatment of insulin resistance.AMPK 1 is a heterotrimeric serine/threonine protein kinase composed of a catalytic ␣ subunit and non-catalytic  and ␥ subunits (1, 2). The mammalian genome contains seven AMPK genes encoding two ␣, two , and three ␥ isoforms. AMPK signaling is elicited by cellular stresses that deplete ATP (and consequently elevate AMP) by either inhibiting ATP production (e.g. hypoxia) or accelerating ATP consumption (e.g. muscle contraction). AMPK is activated allosterically by AMP and through phosphorylation of Thr 172 in the ␣ subunit by an upstream AMPK kinase, the tumor-suppressor protein kinase LKB1 (3, 4). AMPK is likely to be important for diverse functions in many cell types, but particular interest has been focused on elucidating the role of AMPK in the regulation of lipid and carbohydrate metabolism in skeletal muscle (5-10). AMPK activity has been correlated with an increase in glucose uptake and fatty acid oxidation and an inhibition of glycogen synthase activity and fatty acid synthesis. Exercise, as well as skeletal muscle contractions in vitro, leads to AMPK activation. Pharmacological activation of AMPK also can be achieved using 5-aminoimidazole-4-carboxamide-1--D-ribonucleoside (AICAR). Once taken up by the cell, AICAR is phosphorylated to 5-aminoimidazole-4-carboxamide riboside monophosphate (ZMP) and mimics effects of AMP on AMPK (1, 2). AMPK function is closely related to glycogen storage. AMPK phosphorylates glycogen synthase in vitro (11) and co-immunoprecipitates with glycogen synthase and glycogen phosphorylase from skeletal muscle (12). Mutations of the ␥3 or ␥2 subunit, respectively, affect glycogen storage in pigs (13, 14) or glycogen storage associated with cardiac abnormalities in humans (15). The recent identification of a glycogen-binding domain in the AMPK 1 subunit provides a molecular relationship between AMPK and glycogen (16,17). The formation of heterotrimers appears to be...
Osteoinduction is the process by which osteogenesis is induced. It is a phenomenon regularly seen in any type of bone healing process. Osteoinduction implies the recruitment of immature cells and the stimulation of these cells to develop into preosteoblasts. In a bone healing situation such as a fracture, the majority of bone healing is dependent on osteoinduction. Osteoconduction means that bone grows on a surface. This phenomenon is regularly seen in the case of bone implants. Implant materials of low biocompatibility such as copper, silver and bone cement shows little or no osteoconduction. Osseointegration is the stable anchorage of an implant achieved by direct bone-to-implant contact. In craniofacial implantology, this mode of anchorage is the only one for which high success rates have been reported. Osseointegration is possible in other parts of the body, but its importance for the anchorage of major arthroplasties is under debate. Ingrowth of bone in a porous-coated prosthesis may or may not represent osseointegration.
Four different surface modifications were designed. Forty screw-shaped implants were divided into 4 groups, 10 screws in each. Every screw was prepared with 2 different surface topographies. The surface topography was measured with a confocal laser scanning profilometer and the surface roughness was characterized using 1 height, 1 spatial and 1 hybrid descriptive parameter. After 12 weeks in rabbit bone all screws were histomorphometrically evaluated. Blasted surfaces demonstrated more bone in contact to implant surface compared with turned surfaces. Most bone in close contact to implant surface was found for a surface blasted with 75 microns sized particles, numerically characterized with an average height deviation (Sa) of 1.4 microns, an average wavelength (Scx) of 11.6 microns and a developed surface area ratio (Sdr) of 1.5.
DPBB particles were found to be well integrated in lamellar bone, after sinus floor augmentation in humans, showing no significant changes in particle size after 11 years. To cite this article: Mordenfeld A, Hallman M, Johansson CB, Albrektsson T. Histological and histomorphometrical analyses of biopsies harvested 11 years after maxillary sinus floor augmentation with deproteinized bovine and autogenous bone.
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