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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Histologic analysis of bone parameters. (a–d) The chondro-osseous juncti...
Histologic analysis of bone parameters. (a–d) The chondro-osseous junction of the femur from wild-type; PTH–/–; PTHrP–/–; and PTH–/–, PTHrP–/– mice immunostained for eNOS. (e–h) TUNEL reaction to detect apoptotic osteoblasts and osteocytes, performed as described in Methods. (i–l) Sections stained histochemically for TRAP to detect osteoclasts. Scale bars in d, h, and l, represent 50 μm. (m) The eNOS-immunopositive area as a percentage of each field in the chondro-osseous junction was determined by image analysis as described in Methods and is presented as the mean ± SEM of triplicate determinations. (n) The numbers of apoptotic osteoblasts or osteocytes per field as determined by TUNEL assay were quantitated by image analysis and are presented as mean ± SEM of triplicate determinations. (o) The number of TRAP-positive osteoclasts per field was determined by image analysis. Data is presented as mean ± SEM. (p) The mean size of TRAP-positive osteoclasts was also determined in the same fields by image analysis and is presented as the mean ± SEM of triplicate determinations. *P < 0.05 relative to the wild-type mice. #P < 0.05, PTH–/–, PTHrP–/– mice relative to PTHrP–/– mice or PTH–/– mice.