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Cellular and molecular strategies for studying the regulation of bone resorption using the toothless (osteopetrotic) mutation in the rat
P.R. Odgren1, D.C. Hermey2, S.N. Popoff3 and S.C. Marks Jr1
1Department of Cell Biology, University of Massachusetts, Medical School, Worcester, MA,
2Department of Anatomy, Nova Southeastern University, Ft. Launderdale, FL and
3Department of Anatomy and Cell Biology, Temple University, School of Medicine, Philadelphia, PA, USA
Offprint requests to: Dr. Sandy C. Marks Jr, Department of Cell Biology, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, MA 01655, USA
Summary. The division of labor among cells of the
skeleton is distinct and diverse and the regulation of
these cells is interdependent. Osteoclasts are the cellular
source of bone resorption and signals for their
development and activation come, at least in part, from
bone and other cells in the local environment. Studies of
isolated cells have identified some factors in the
developmental cascade of osteoclasts but there is little
understanding of the sequence and local concentrations,
not to mention other factors, needed for both the
development of competent osteoclasts and for
coordinated bone resorption. We review the skeletal
biology of one osteopetrotic mutation in the rat,
toothless, in which bone resorption is severely reduced
because of a failure in the development and function of
osteoclasts. Furthermore, we review the advantages and
limitations of a relatively new method, differential
display of mRNA (DO), that identifies differences in
gene expression in two or more populations of cells. We
present a strategy and preliminary data for the
application of DO to this mutation . We propose
that application of this method to these and other
skeletal diseases, with the appropriate controls and
confirmations, will provide data about pathogenetic
pathways and has a high probability for identifying new
regulators of skeletal development and turnover. Histol Histopathol 12, 1151-1157
(1997)
Key words: Osteoclast, Molecular biology, Bone
resorption, Regulation, Rat
DOI: 10.14670/HH-12.1151
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