PMID- 21869564
OWN - NLM
STAT- MEDLINE
DCOM- 20120103
LR  - 20190911
IS  - 1347-8648 (Electronic)
IS  - 1347-8613 (Linking)
VI  - 117
IP  - 1
DP  - 2011
TI  - Inhibitory effect of chlorpromazine on RANKL-induced osteoclastogenesis in mouse 
      bone marrow cells.
PG  - 54-62
AB  - Chlorpromazine (CPZ), the first widely used phenothiazine tranquilizer, is shown 
      to inhibit the action of intracellular calmodulin (CaM) and bone resorption in 
      vivo and in vitro. In this study, CPZ (0.63 - 10 microM) dose-dependently inhibited 
      the formation of tartrate-resistant acid phosphatase (TRAP) staining-positive 
      osteoclast-like cells in mouse bone marrow cells (BMCs) treated with 
      1alpha,25(OH)(2)D(3) (10 nM) or soluble receptor activator of nuclear factor-kappaB 
      ligand (s-RANKL) (20 ng/ml). Expressions of mRNA for the nuclear factor of 
      activated T-cells c1 (NFATc1), a key regulator of osteoclast differentiation; 
      dendritic cell-specific transmembrane protein (DC-STAMP), an essential protein 
      for cell-cell fusion; and characteristic markers of osteoclasts such as TRAP, 
      cathepsin K, carbonic anhydrase II, and calcitonin receptor in BMCs were 
      up-regulated by s-RANKL and decreased by the addition of CPZ (5 microM) or the 
      selective CaM antagonist W7, but not the inactive analog W5. The general CaM 
      kinase (CaMK) inhibitor KN-93 and CaM-dependent phosphatase calcineurin inhibitor 
      FK-506 also inhibited s-RANKL-induced osteoclastogenesis. Phenothiazines such as 
      CPZ, trifluoperazine (TFPZ), and promethazine (PMZ) inhibited s-RANKL-induced 
      osteoclast-like cell formation in mouse BMCs. Osteoclastogenesis inhibitory 
      effects decreased in the order of TFPZ, CPZ, PMZ, depending on their anti-CaM 
      potency. These findings suggest that CPZ inhibits RANKL-induced 
      osteoclastogenesis by its anti-CaM action.
FAU - Kawamura, Hiroharu
AU  - Kawamura H
AD  - Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Japan.
FAU - Arai, Michitsugu
AU  - Arai M
FAU - Togari, Akifumi
AU  - Togari A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110826
PL  - Japan
TA  - J Pharmacol Sci
JT  - Journal of pharmacological sciences
JID - 101167001
RN  - 0 (DNA Primers)
RN  - 0 (RANK Ligand)
RN  - 0 (Tnfsf11 protein, mouse)
RN  - U42B7VYA4P (Chlorpromazine)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Bone Marrow Cells/*drug effects
MH  - Cell Differentiation/drug effects
MH  - Chlorpromazine/*pharmacology
MH  - DNA Primers
MH  - Male
MH  - Mice
MH  - Osteoclasts/cytology/*physiology
MH  - RANK Ligand/*physiology
EDAT- 2011/08/27 06:00
MHDA- 2012/01/04 06:00
CRDT- 2011/08/27 06:00
PHST- 2011/08/27 06:00 [entrez]
PHST- 2011/08/27 06:00 [pubmed]
PHST- 2012/01/04 06:00 [medline]
AID - JST.JSTAGE/jphs/11006FP [pii]
AID - 10.1254/jphs.11006fp [doi]
PST - ppublish
SO  - J Pharmacol Sci. 2011;117(1):54-62. doi: 10.1254/jphs.11006fp. Epub 2011 Aug 26.