Parathyroid hormone and prostaglandin E-2 preferentially increase luciferase levels in bone of mice harboring a luciferase transgene controlled by elements of the pro-alpha 1(I) collagen promoter

Type 1 collagen is the major extracellular protein in bone, tendons, ligame nts, and skin. DNA elements of the mouse pro-alpha 1 (I) collagen promoter were shown to drive the bone-selective expression of a luciferase transgene , We examined whether this expression can be used to evaluate the effect of anabolic agents on bone formation in vivo. Treatment of either intact male s, intact females, or ovariectomized (ovx) mice with 80 mu g/kg/day of huma n parathyroid hormone (hPTH), for 5 to 11 days increased luciferase levels in tibiae by two- to threefold compared with vehicle-treated mice. The incr eases were tissue specific, as no changes in skin luciferase expression wer e observed. Treatment with prostaglandin E-2, a potent bone anabolic agent, for 11 days also increased expression of the transgene in bone, but not in skin, Treatment with dihydrotestosterone (DHT) for 11 days increased lucif erase activity in skin, but not in bone. Histomorphometric analysis reveale d that 28-day treatment with PTH increased bone formation; 60-day treatment of OVX mice with DHT did not. These findings show a correlation between bo ne formation and the expression of a transgene driven by DNA elements of th e mouse pro-alpha 1 (I) collagen promoter, suggesting that this expression can be used as an indicator and provide a faster readout for the ability of agents to stimulate bone formation in this mouse strain. (C) 2000 by Elsev ier Science Inc. All rights reserved.