Release of Prostaglandin E1 from N-(2-Hydroxypropyl)methacrylamide Copolymer Conjugates by Bone Cells
✍ Scribed by Huaizhong Pan; Jihua Liu; Yuanyi Dong; Monika Sima; Pavla Kopečková; Maria Luisa Brandi; Jindřich Kopeček
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 252 KB
- Volume
- 8
- Category
- Article
- ISSN
- 1616-5187
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✦ Synopsis
Abstract
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.
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