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J Biol Chem, Vol. 275, Issue 15, 11082-11091, April 14, 2000
From the Department of Biomedical Engineering, The Lerner Research
Institute of The Cleveland Clinic Foundation, Cleveland, Ohio 44195 and
the Parathyroid hormone (PTH-(1-34)) potently
suppresses apatite deposition in osteoblastic cultures. These
inhibitory effects are mediated through signaling events following PTH
receptor binding. Using both selective inhibitors and activators of
protein kinase A (PKA), this study shows that a transient activation of
PKA is sufficient to account for PTH's inhibition of apatite
deposition. This inhibition is not a result of reduced cell
proliferation, reduced alkaline phosphatase activity, increased
collagenase production, or lowering medium pH. Rather, data suggest a
functional relationship between matrix assembly and apatite deposition
in vitro. Bone sialoprotein (BSP) and apatite co-localize
in the extracellular matrix of mineralizing cultures, with matrix
deposition of BSP temporally preceding that of apatite. Transient
activation of PKA by either PTH-(1-34) or short term cAMP analog
treatment blocks the deposition of BSP in the extracellular matrix
without a significant reduction in the total amount of BSP synthesized
and secreted. This effect is reversible after allowing the cultures to
recover in the absence of PKA activators for several days. Thus, a
transient activation of PKA may suppress mineral deposition in
vitro as a consequence of altering the assembly of an
extracellular matrix permissive for apatite formation.
Reversible Suppression of in Vitro Biomineralization
by Activation of Protein Kinase A*
,, and Department of Orthopaedic Surgery, College of
Medicine, The University of Iowa, Iowa City, Iowa 52242
*
This work was funded by the Roy J. Carver Charitable
Trust Fund (University of Iowa), a Rhone-Poulenc Rorer Research Award from the Orthopaedic Research and Education Foundation (to R. J. M.),
and The Lerner Research Institute of The Cleveland Clinic Foundation.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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