



@article {2443,
	title = {Recombinant glucocerebrosidase uptake by Gaucher disease human osteoblast culture model},
	journal = {Blood Cells, Molecules, and DiseasesBlood Cells Mol. Dis.},
	volume = {35},
	year = {2005},
	note = {Cited By (since 1996): 3Export Date: 21 November 2012Source: ScopusCODEN: BCMDFdoi: 10.1016/j.bcmd.2005.07.009PubMed ID: 16125984Language of Original Document: EnglishCorrespondence Address: Lamghari, M.; INEB-Instituto de Engenharia Biom{\'e}dica, Laborat{\'o}rio de Biomateriais, R. Campo Alegre 823, 4150-180 Porto, Portugal; email: lamghari@ineb.up.ptChemicals/CAS: conduritol b epoxide, 6090-95-5; imiglucerase, 154248-97-2; iodine 125, 14158-31-7, 22822-81-7; conduritol epoxide, 6090-95-5; Glucosylceramidase, EC 3.2.1.45; Inositol, 6917-35-7; Recombinant ProteinsTradenames: cerezyme, GenzymeManufacturers: GenzymeReferences: Beutler, E., Grabowski, G., Gaucher disease (1995) The Metabolic and Molecular Bases of Inherited Disease, 2, pp. 2641-2661. , C.R. Scriber A.L. Beaudet W.S. Sly 7th ed. McGraw-Hill New York, NY;Beutler, E., Enzyme replacement in Gaucher disease (2004) PLoS Med., 1 (2), p. 21; 
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},
	month = {2005///},
	pages = {348 - 354},
	abstract = {Bone lesions are a major cause of morbidity in Gaucher disease (GD) type I. Enzyme replacement therapy (ERT) has been successful in treating many symptoms of type I GD but skeletal response lags behind. Local exogenous glucocerebrosidase supplementation in bone lesions via a drug delivery system may overcome this limitation. Although local enzyme supplementation aims to target lipid-engorged macrophages (Gaucher Cells) in bone compartment, enzyme uptake by osteoblasts is not excluded. To investigate the ability of human osteoblasts to internalize recombinant glucocerebrosidase (rGCR), we have used an artificial GD human osteoblasts cell culture system. MG63 human osteoblasts were treated with conduritol B epoxide (CBE) to induce complete and prolonged inhibition of endogenous glucocerebrosidase activity of cells. rGCR uptake by glucocerebrosidase-inactivated osteoblasts was examined using                        125I-radiolabelling, Western blot analysis and measurement of glucocerebrosidase activity. Analysis of radiolabeled enzyme uptake by CBE treated osteoblasts showed 67.9\% of internalized protein in cell extract. Enzyme internalization was also observed by Western blot analysis where the amount of mature form of glucocerebrosidase protein recognized by the glucocerebrosidase antibody was increased following the administrations of rGCR. Moreover, enzymatic activity measurement showed 23.9\% of glucocerebrosidase activity of control cells. The rGCR internalization by MG63 osteoblast seems to be partially mediated by mannose receptors. These data provide evidence that MG63 human osteoblasts are able to internalize rGCR. {\textcopyright} 2005 Elsevier Inc. All rights reserved.
},
	keywords = {article, Cell culture, cell extract, Cells, Cultured, conduritol b epoxide, controlled study, drug activity, drug uptake, enzyme activity, enzyme antibody, Enzyme inhibition, Enzyme uptake, epoxide, Gaucher disease, Glucocerebrosidase, Glucosylceramidase, human, human cell, Humans, imiglucerase, Inositol, internalization, iodine 125, isotope labeling, mannose receptor, osteoblast, Osteoblasts, priority journal, Recombinant Proteins, unclassified drug, Western blotting},
	isbn = {10799796 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-27744461413\&partnerID=40\&md5=575b4d8cc3f6e5b8e846cf6de71852b3},
	author = {Lamghari, M. and Barrias, C.C. and S{\'a} Miranda, C. and Barbosa, M.A.}
}
