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Characteristics of clodronate-induced apoptosis in osteoclasts and macrophages

, : Characteristics of clodronate-induced apoptosis in osteoclasts and macrophages. Molecular Pharmacology 50(5): 1127-1138

Bisphosphonates (BPs), such as clodronate and pamidronate, are inhibitors of bone resorption and are used on a widespread basis in the treatment of hyper-resorptive bone diseases. At the cellular level, BPs inhibit osteoclasts, but the precise molecular mechanisms are unclear. BPs have also been shown to affect the survival of macrophages, cells ontogenetically related to osteoclasts. We show that both clodronate and pamidronate induce apoptosis in isolated osteoclasts. Clodronate, when administered in liposomes, also induced apoptosis in rat peritoneal macrophages in vitro and in liver macrophages of mice in vivo but not in murine macrophage-like RAW-264 cells. The subcellular localization and staining intensity of Bcl-2, an anti-apoptotic protein known to protect several cell types against drug-induced apoptosis, were similar in RAW-264 and peritoneal macrophage cells, as revealed by immunofluorescence. The clodronate-induced apoptotic pathway was further characterized in isolated osteoclasts cultured on glass coverslips through the use of clodronate-containing liposomes and several inhibitors of the apoptotic cascade. None of the agents tested could totally prevent clodronate-induced osteoclast death. Partial protection was, however, obtained by the addition of staurosporine or homocysteine. The results suggest that primarily cytoplasmic, protein kinase C-activated mechanisms are involved in the execution of clodronate-induced apoptosis of osteoclasts.


PMID: 8913344

Other references

Brill, F.E., 1966: The Health Research Council of New York City. Public Health Reports 81(1): 17-20

Hagiladi, A.Z.v, O., 1986: Use of antitranspirants for control of powdery mildew on field grown roses. Journal of environmental horticulture 4(2): 65-68

Mahmoud, L.H.; Basiouny, S.O.; Dawoud, H.A., 2002: Treatment of experimental heterophyiasis with two plant extracts, areca nut and pumpkin seed. The effect of aqueous extracts of areca nut and pumpkin seeds in the treatment of puppies experimentally infected with Heterophyes heterophyes gave promising results. Puppies were infected through feeding on the muscles of Mugil sp. fish containin...

Holm V.A.; Knox W.E., 1979: Physical growth in phenyl ketonuria part 1 a retrospective study. A retrospective cross-sectional survey of phenylketonuria (PKU) was conducted in 1967. Questionaires on 693 patients, clinically thought to have PKU, were reanalyzed to obtain information on growth in height and head circumference in patients with...

Hirose, M.; Takeda, E.; Ninomiya, T.; Kuroda, Y.; Miyao, M., 1986: Inhibitory effect of dipyridamole on the growth of various human hematologic malignant cell lines. The extent of use and role of the salvage pathway of pyrimidine metabolism for DNA biosynthesis in the growth of human hematologic malignant cultured cell lines were studied by examining the effect of dipyridamole, an effective blocker of this sal...

Ersfeld, K., 2004: Fiber-FISH: fluorescence in situ hybridization on stretched DNA. High-resolution fluorescence in situ hybridization (FISH) on deproteinized, stretched DNA prepared by in situ extraction of whole cells immobilized on microscope glass slides allows the visualization of individual genes or other small DNA elements...

Tobias, PV., 1975: New African evidence on the dating and the phylogeny of the Plio-Pleistocene Hominidae. Conference int. Ass. quatern. Res, 9: 289-296

Janda, V., 1931: Ueber die Phototaxis der Larven und Imagines von Anthrenus museorum L. Zoologischer Anzeiger Leipzig, 96: 77-84

Anonymous, 2001: 6th Congress of Therapy and Neurology: Headaches. Paris, France, 3-4 December 1999. Proceedings. Revue Neurologique 156 Suppl 4: 4s4-112

Rehfeldt C.; Fiedler I.; Wegner J., 1987: Changes in muscle microstructure in laboratory mice cattle and pigs during growth. The changes of number, size and types of muscle fibres during growth have been examined by histological methods using muscles of laboratory mice, pigs and cattle. Postnatal growth of muscle was found to be due generally to the hypertrophy of fibre...