Parathyroid hormone is essential for normal fetal bone formation
Dengshun Miao, Bin He, Andrew C. Karaplis, David Goltzman
Dengshun Miao, Bin He, Andrew C. Karaplis, David Goltzman
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Article Endocrinology

Parathyroid hormone is essential for normal fetal bone formation

Abstract

Parathyroid hormone (PTH) is a potent pharmacologic inducer of new bone formation, but no physiologic anabolic effect of PTH on adult bone has been described. We investigated the role of PTH in fetal skeletal development by comparing newborn mice lacking either PTH, PTH-related peptide (PTHrP), or both peptides. PTH-deficient mice were dysmorphic but viable, whereas mice lacking PTHrP died at birth with dyschondroplasia. PTH-deficient mice uniquely demonstrated diminished cartilage matrix mineralization, decreased neovascularization with reduced expression of angiopoietin-1, and reduced metaphyseal osteoblasts and trabecular bone. Compound mutants displayed the combined cartilaginous and osseous defects of both single mutants. These results indicate that coordinated action of both PTH and PTHrP are required to achieve normal fetal skeletal morphogenesis, and they demonstrate an essential function for PTH at the cartilage-bone interface. The effect of PTH on fetal osteoblasts may be relevant to its postnatal anabolic effects on trabecular bone.

Authors

Dengshun Miao, Bin He, Andrew C. Karaplis, David Goltzman

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Quantitation of bone parameters. (a–d) Undecalcified sections of femurs ...
Quantitation of bone parameters. (a–d) Undecalcified sections of femurs stained with von Kossa stain as described in Methods and photographed at a magnification of 25. T, trabecular bone (red square). C, cortical bone (arrows). (e–h) Primary spongiosa from wild-type; PTH–/–; PTHrP–/–; and PTH–/–, PTHrP–/– mice stained with H&E. (i–l) Diaphyseal region from wild-type and mutant mice stained with H&E. (m and n) The cortical thickness and trabecular bone volume were measured from three each of the wild-type; PTH–/–; PTHrP–/–; and PTH–/–, PTHrP–/– mice and presented as mean ± SEM. (o) The number of osteoblasts per field were counted in triplicate in the primary spongiosa of H&E-stained femurs of the mice and presented as mean ± SEM. *P < 0.05, mutant mice relative to wild-type mice. #P < 0.05, compound mutant mice relative to PTH–/– mice or PTHrP–/– mice.