A novel inhibitory mechanism of nitrogen-containing bisphosphonate on the activity of Cl− extrusion in osteoclasts

• Published in: Naunyn-Schmiedeberg's archives of pharmacology Vol. 386; no. 7; pp. 589 - 598
• Main Authors: Ohgi, Kimiko, Kajiya, Hiroshi, Okamoto, Fujio, Nagaoka, Yoshiyuki, Onitsuka, Tokuya, Nagai, Atsushi, Sakagami, Ryuji, Okabe, Koji
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.07.2013
• Subjects: Alkyl and Aryl Transferases - antagonists & inhibitors; Animals; Biomedical and Life Sciences; Biomedicine; Bone Marrow Cells - cytology; Cell Line; Cells, Cultured; Chlorides - physiology; Diphosphonates - chemistry; Diphosphonates - pharmacology; Diterpenes - pharmacology; Gene Silencing; Geranyltranstransferase - antagonists & inhibitors; Geranyltranstransferase - genetics; Geranyltranstransferase - metabolism; Male; Mice; Neurosciences; Nitrogen - chemistry; Original Article; Osteoclasts - drug effects; Osteoclasts - physiology; Pharmacology/Toxicology; RNA, Small Interfering - genetics; Xenopus; Zoledronic acid; Farnesyl diphosphate synthase; Osteoclasts; Chloride current; Bisphosphonates

Nitrogen-containing bisphosphonates have been well known to be inhibited farnesyl diphosphate synthase (FDPS), an enzyme in mevalonic acid metabolism, resulting in disturbance in polymerization of cytoskeleton structure in bone resorption and promotion of apoptosis in mature osteoclasts. Although bi...