Parathyroid hormone-related peptide is required for increased trabecular bone volume in parathyroid hormone-null mice.
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 trabecular bone volume with diminished bone turnover. PTHrP haploinsufficiency 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.
Miao
Dengshun
D
Calcium Research Laboratory of the McGill University Health Center, Montréal, Québec, Canada.
Li
Jiarong
J
Xue
Yingben
Y
Su
Hanyi
H
Karaplis
Andrew C
AC
Goltzman
David
D
D000818:Animals; D015519:Bone Density; D001862:Bone Resorption; D006023:Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000502:physiology; D010012:Osteogenesis; D053244:Osteoprotegerin; D010281:Parathyroid Hormone / Q000502:physiology*; D044162:Parathyroid Hormone-Related Protein / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor
D006023:Glycoproteins; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506031:Tnfrsf11b protein, mouse