Parathyroid hormone-related peptide is required for increased trabecular bone volume in parathyroid hormone-null mice

Abstract

We investigated the relative contributions of PTH and PTHrP to the skeletal phenotype of mice deficient in PTH (PTH-/-). PTH-/- mice and PTH-/- mice lacking one allele encoding PTHrP (PTH -/-PTHrP+/-) were compared. Both mutants displayed similar biochemical abnormalities of hypoparathyroidism, but skeletal PTHrP mRNA and protein were decreased in PTH-/-PTHrP+/- mice. PTH -/- mice had increased trabecnlar bone volume with diminished bone turnover. PTHrP haploinsufficieney reduced trabecular bone of the PTH -/- mice to levels below those in wild-type animals by decreasing osteoprogenitor cell recruitment, enhancing osteoblast apoptosis, and diminishing bone formation. The results show that the increased trabecular bone volume in PTH-deficient mice is due to diminished PTH-induced osteoclastic bone resorption and persistent PTHrP-stimulated osteoblastic bone formation. They also illustrate the changing role of PTHrP during bone development, demonstrate its bone-forming function in the postnatal state, and support its pharmacological potential as an anabolic agent.