title: RANK ligand expression in heat shock factor-2 deficient mouse bone marrow stromal/preosteoblast cells.
abstract: Heat Shock Proteins (HSP) are molecular chaperones activated upon cellular stress/stimuli. HSP gene expression is regulated by Heat Shock Factors (HSF). We have recently demonstrated a functional role for heat shock factor-2 (HSF-2) in fibroblast growth factor-2 (FGF-2)-induced RANK ligand (RANKL), a critical osteoclastogenic factor expression on stromal/preosteoblast cells. In the present study, we show that FGF-2 treatment did not induce RANKL expression in HSF-2-/-stromal/preosteoblast cells. Interestingly, HSF-2 deficiency resulted in rapid induction of alkaline phosphatase (ALP) activity and osteocalcin mRNA expression in these cells. Furthermore, FGF-2 did not induce osteoclast formation in co-culture of normal mouse spleen cells and HSF-2-/-stromal/preosteoblast cells. Electron microscopy analysis demonstrated that osteoclasts from HSF-2-/-mice have poorly developed ruffled borders. These data further confirm that HSF-2 plays an important role in FGF-2-induced RANKL expression in stromal/preosteoblast cells. HSF-2 deficiency has pleotropic effects on gene expression during osteoblast differentiation and osteoclastogenesis in the bone microenvironment. Novel therapeutic agents that modulate HSF-2 activation may have therapeutic utility against increased levels of FGF-2 and bone destruction associated with pathologic conditions.
authors.affiliation: Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Sawara-ku, Fukuoka, 814-0193, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kajiya
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ito
authors.forename: Hayato
authors.initials: H
authors.lastname: Ohshima
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Kenmotsu
authors.forename: William L
authors.initials: WL
authors.lastname: Ries
authors.forename: Ivor J
authors.initials: IJ
authors.lastname: Benjamin
authors.forename: Sakamuri V
authors.initials: SV
authors.lastname: Reddy
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism* / Q000648:ultrastructure; D010010:Osteoclasts / Q000378:metabolism / Q000648:ultrastructure; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D017154:Stromal Cells / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486699:Hspb2 protein, mouse; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D016222:Fibroblast Growth Factor 2; D000469:Alkaline Phosphatase