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Abstract
Parathyroid hormone (PTH) is a potent stimulator of osteoblastic cell function in
vitro and bone resorption and formation in vivo; however, the details of the molecular
mechanism(s) responsible for PTH action and the regulation of gene expression in response
to PTH remain unknown. In this study, we employed an mRNA differential display (DRD)
approach to examine the initial events in gene expression in human osteoblast-like
SaoS-2/B10 cells exposed to 10(-7) mol/L bPTH(1-34). This approach identified several
differentially regulated mRNA species, including a novel paired-class homeobox protein,
osteoblast-specific factor-2 (OSF-2), and a unique clone with no known sequence homology
(clone G18). G18 is a previously unidentified human gene, expressed in a wide variety
of human tissues, including heart, brain, placenta, skeletal muscle, and kidney, and
is regulated by PTH in osteoblastic cells in vitro. This mRNA appears to be the product
of a single gene, which is alternatively spliced to produce multiple transcript sizes
observed in several tissues, except bone and bone-derived cells, in which a single
predominant approximately 1.8 kb transcript is observed. Our study has identified
several genes that have expression altered significantly by treatment with bPTH(1-34),
and which may provide insight into the immediate effects of PTH on osteoblast-like
cells and ultimately on the mechanism of action and bioactivity of PTH.