Parathyroid hormone is essential for normal fetal bone formation
Dengshun Miao, … , Andrew C. Karaplis, David Goltzman
Dengshun Miao, … , Andrew C. Karaplis, David Goltzman
Published May 1, 2002
Citation Information: J Clin Invest. 2002;109(9):1173-1182. https://doi.org/10.1172/JCI14817.
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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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Assessment of indices of chondrocyte proliferation, apoptosis, and diffe...
Assessment of indices of chondrocyte proliferation, apoptosis, and differentiation. (a–d) Paraffin-embedded sections of tibiae from wild-type; PTH–/–; PTHrP–/–; and PTH–/–, PTHrP–/– mice were immunostained for PCNA as described in Methods. (e–h) Sections were stained for apoptosis using TUNEL. (i–l) Sections were immunostained for type X collagen (Col X). Scale bars in d, h, and l represent 50 μm. (m) The numbers of PCNA-positive chondrocytes, of TUNEL-positive chondrocytes, and of total chondrocytes per field were determined by image analysis; the PCNA-positive and TUNEL-positive percentages of total chondrocytes counted are presented as the mean ± SEM of triplicate determinations. (n) Immunostaining for type X collagen was performed as described in Methods, and the immunopositive area as a percentage of the growth plate field was determined. The percent-positive area is presented as mean ± SEM of triplicate determinations. *P < 0.05 in the mutant mice relative to the wild-type mice.