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This version published online on April 16, 2004
Endocrinology, doi:10.1210/en.2003-1695
A more recent version of this article appeared on August 1, 2004
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Submitted on December 14, 2003
Accepted on April 1, 2004

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

Dengshun Miao, Jiarong Li, Yingben Xue, Hanyi Su, Andrew C. Karaplis, and David Goltzman*

Calcium Research Laboratory of the McGill University Health Centre, Lady Davis Institute for Medical Research of the Sir Mortimer B. Davis - Jewish General Hospital, and the Department of Medicine, McGill University, Montreal, QC, Canada

* To whom correspondence should be addressed. E-mail: david.goltzman{at}mcgill.ca.

We investigated the relative contributions of parathyroid hormone (PTH) and PTH related peptide (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 trabecular bone volume with diminished bone turnover. PTHrP haploinsufficiency reduced trabecular bone of the PTH-/- mice to levels below wild-type 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 pharmacologic potential as an anabolic agent.
Key words: Hypoparathyroidism • Bone formation and resorption • PTH and PTHrP




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