Nejvíce citovaný článek - PubMed ID 11697801
Bisphosphonates (BPs) are compounds resembling the pyrophosphate structure. BPs bind the mineral component of bones. During the bone resorption by osteoclasts, nitrogen-containing BPs are released and internalized, causing an inhibition of the mevalonate pathway. As a consequence, osteoclasts are unable to execute their function. Alendronate (ALN) is a bisphosphonate used to treat osteoporosis. Its administration could be associated with adverse effects. The purpose of this study is to evaluate four different ALN concentrations, ranging from 10-6 to 10-10 M, in the presence of different combinations of M-CSF and RANKL, to find out the effect of low ALN concentrations on osteoclastogenesis using rat and human peripheral blood mononuclear cells. The cytotoxic effect of ALN was evaluated based on metabolic activity and DNA concentration measurement. The alteration in osteoclastogenesis was assessed by the activity of carbonic anhydrase II (CA II), tartrate-resistant acid phosphatase staining, and actin ring formation. The ALN concentration of 10-6 M was cytotoxic. Low ALN concentrations of 10-8 and 10-10 M promoted proliferation, osteoclast-like cell formation, and CA II activity. The results indicated the induction of osteoclastogenesis with low ALN concentrations. However, when high doses of ALN were administered, their cytotoxic effect was demonstrated.
- Klíčová slova
- M-CSF, RANKL, alendronate, osteoclastogenesis,
- MeSH
- aktiny metabolismus MeSH
- alendronát farmakologie MeSH
- barvení a značení MeSH
- DNA metabolismus MeSH
- faktor stimulující kolonie makrofágů farmakologie MeSH
- karboanhydrasa II metabolismus MeSH
- krysa rodu Rattus MeSH
- kyselá fosfatasa rezistentní k tartarátu metabolismus MeSH
- leukocyty mononukleární účinky léků metabolismus MeSH
- lidé MeSH
- ligand RANK farmakologie MeSH
- osteogeneze účinky léků MeSH
- osteoklasty účinky léků enzymologie metabolismus MeSH
- proliferace buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- aktiny MeSH
- alendronát MeSH
- DNA MeSH
- faktor stimulující kolonie makrofágů MeSH
- karboanhydrasa II MeSH
- kyselá fosfatasa rezistentní k tartarátu MeSH
- ligand RANK MeSH