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Release of Prostaglandin E 1 from N ‐(2‐Hydroxypropyl)methacrylamide Copolymer Conjugates by Bone Cells
Author(s) -
Pan Huaizhong,
Liu Jihua,
Dong Yuanyi,
Sima Monika,
Kopečková Pavla,
Brandi Maria Luisa,
Kopeček Jindřich
Publication year - 2008
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.200700338
Subject(s) - methacrylamide , chemistry , conjugate , endocytosis , cleavage (geology) , prostaglandin e , cathepsin d , cell culture , osteoclast , cathepsin , biochemistry , cell , microbiology and biotechnology , enzyme , in vitro , copolymer , biology , acrylamide , mathematical analysis , paleontology , genetics , mathematics , organic chemistry , fracture (geology) , polymer
Bone‐targeting N ‐(2‐hydroxypropyl)methacrylamide (HPMA) copolymer‐PGE 1 conjugates, containing cathepsin K sensitive spacers, were incubated with induced osteoclasts and osteoblasts, their precursors, and control non‐skeletal cells. The release of PGE 1 was monitored by an HPLC assay. In both murine and human cell lines, osteoclasts appeared to be the most active cells in the cleavage (PGE 1 release). Incubation with osteoblasts also resulted in fast PGE 1 release, whereas precursor and control cells released PGE 1 with a substantially slower rate than bone cells (apparently through ester bond cleavage). Experiments in the presence of inhibitors revealed that other enzymes, in addition to cathepsin K, were participating in the cleavage of the conjugate. Confocal fluorescence studies exposed internalization of the conjugate by endocytosis with ultimate localization in the lysosomal/endosomal compartment.