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RANK ligand expression in heat shock factor-2 deficient mouse bone marrow stromal/preosteoblast cells. J Cell Biochem 2006 Apr 15;97(6):1362-9

Date

12/21/2005

Pubmed ID

16365894

DOI

10.1002/jcb.20737

Scopus ID

2-s2.0-33645657652   8 Citations

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.

Author List

Kajiya H, Ito M, Ohshima H, Kenmotsu S, Ries WL, Benjamin IJ, Reddy SV

Author

Ivor J. Benjamin MD Center Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Alkaline Phosphatase
Animals
Bone Marrow
Carrier Proteins
Cell Differentiation
Cells, Cultured
Fibroblast Growth Factor 2
HSP27 Heat-Shock Proteins
Heat-Shock Proteins
Membrane Glycoproteins
Mice
Osteoblasts
Osteoclasts
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B
Stromal Cells
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a