title: Inhibition of bone resorption by econazole in rat osteoclast-like cells through suppressing TRPV5.
abstract: Osteoclasts are primary bone resorption cells and intervention in osteoclast activation is considered an effective therapeutic approach to treatment of bone diseases involving osteoclasts. TRPV5 was detected in osteoclasts and it has been thought to take part in the transportation of the degraded calcium in the resorption lacuna, which is essential for bone resorption. The aim of the present study was to examine the effects of a modulator of calcium dynamics, econazole, on the expression of TRPV5 and bone resorption activity in rat osteoclast-like cells (OLCs). OLCs were obtained by co-culturing rat bone marrow cells with osteoblasts and then culturing with different concentrations of econazole (0.01, 0.1, 1.0, 10.0 μmol/L). Cell counting and staining protocols were used to determine whether econazole influenced the survival of OLCs. Expression of TRPV5 in response to econazole treatment was assessed by western blotting. Bone resorption activity of OLCs was determined by measuring the resorption area of dentin slices with a microscope and a digital image analysis system. Additionally, Ca(2+) inside OLCs was tested. We found that econazole inhibited expression of TRPV5 in a dose dependent manner while it had no influence on the survival of OLCs and it therefore inhibited bone resorption activity in rat OLCs. Ca(2+) inside OLCs increased, suggesting a limited compensatory mechanism to make up for inhibition of TRPV5 effects.
authors: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China.
authors: Peng
authors: P
authors: Yan
authors: Tang
authors: T
authors: Li
authors: Meng
authors: M
authors: Bo
authors: Liu
authors: L
authors: Die
authors: Liang
authors: L
authors: Xing
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001862:Bone Resorption / Q000188:drug therapy*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects* / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004464:Econazole / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000187:drug effects* / Q000235:genetics
chemical_list: D015220:Calcium Channels; D050916:TRPV Cation Channels; C492241:TRPV5 protein, rat; D004464:Econazole; D002118:Calcium