Identification of a novel parathyroid hormone-responsive gene in human osteoblastic cells

Parathyroid hormone (PTH) is a potent stimulator of osteoblastic cell funct ion in vitro and bone resorption and formation in vivo; however, the detail s of the molecular mechanism(s) responsible for PTH action and the regulati on 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 expose d to 10(-7) mol/L bPTH(1-34). This approach identified several differential ly regulated mRNA species, including a novel paired-class homeobox protein, osteoblast-specific factor-2 (OSF-2), and a unique clone with no known seq uence homology (clone G18), G18 is a previously unidentified human gene, ex pressed in a wide variety of human tissues, including heart, brain, placent a, skeletal muscle, and kidney, and is regulated by PTH in osteoblastic cel ls in vitro. This mRNA appears to be the product of a single gene, which is alternatively spliced to product! multiple transcript sizes observed in se veral tissues, except bone and bone-derived cells, in which a single predom inant similar to 1.8 kb transcript is observed. Our study has identified se veral genes that have expression altered significantly by treatment with bP TH(1-34), and which may provide insight into the immediate effects of PTH o n osteoblastlike cells and ultimately on the mechanism of action and bioact ivity of PTH. (C) 1999 by Elsevier Science Inc. All rights reserved.