Bisphosphonates: mechanisms of action.
- G. Rodan, H. Fleisch
- MedicineJournal of Clinical Investigation
- 15 June 1996
This review will deal with the mechanisms of action of bisphosphonates and in vitro results, as well as results both in animals and humans, will be integrated in an attempt to deduce the current state of the art.
Therapeutic approaches to bone diseases.
A better understanding of the biology of osteoclasts and osteoblasts is providing opportunities for developing therapeutics to treat diseases of bone, and promoting bone formation with growth factors or hormones is an approach that would be a valuable adjunct therapy for patients receiving inhibitors of bone resorption.
Control of osteoblast function and regulation of bone mass
The skeleton is an efficient 'servo' (feedback-controlled/steady-state) system that continuously integrates signals and responses which sustain its functions of delivering calcium while maintaining…
Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure.
- M. Sato, W. Grasser, G. Rodan
- BiologyJournal of Clinical Investigation
- 1 December 1991
Findings suggest that alendronate binds to resorption surfaces, is locally released during acidification, the rise in concentration stops resOrption and membrane ruffling, without destroying the osteoclasts.
The role of subchondral bone remodeling in osteoarthritis: reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection…
- T. Hayami, M. Pickarski, L. Duong
- Medicine, BiologyArthritis & Rheumatism
- 1 April 2004
Subchondral bone remodeling plays an important role in the pathogenesis of OA and alendronate or other inhibitors of bone resorption could potentially be used as disease-modifying agents in the treatment of Oa.
Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro.
- J. Fisher, M. Rogers, A. Reszka
- Biology, ChemistryProceedings of the National Academy of Sciences…
- 5 January 1999
The hypothesis that alendronate, acting directly on osteoclasts, inhibits a rate-limiting step in the cholesterol biosynthesis pathway, essential for osteoclast function, is supported.
Alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase.
- J. Bergstrom, R. Bostedor, P. Masarachia, A. Reszka, G. Rodan
- Biology, ChemistryArchives of Biochemistry and Biophysics
- 2000
Farnesyl diphosphate synthase is identified as the selective target of alendronate in the mevalonate pathway and shows that this enzyme is inhibited by other N-containing bisphosphonates, but not by clodronate, supporting a different mechanism of action for different bisph phosphonates.
Characterization of a human osteosarcoma cell line (Saos-2) with osteoblastic properties.
The Saos-2 cells possess several osteoblastic features and could be useful as a permanent line of human osteoblast-like cells and as a source of bone-related molecules.
PYK2 in osteoclasts is an adhesion kinase, localized in the sealing zone, activated by ligation of alpha(v)beta3 integrin, and phosphorylated by src kinase.
- L. Dưỡng, P. Lakkakorpi, I. Nakamura, M. Machwate, R. Nagy, G. Rodan
- Biology, ChemistryJournal of Clinical Investigation
- 1 September 1998
Findings suggest that Src-dependent tyrosine phosphorylation of PYK2 is involved in the adhesion-induced formation of the sealing zone, required for osteoclastic bone resorption.
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