Effects of parathyroid hormone (PTH)-related protein and PTH on osteoclasts and osteoclast precursors in vivo

Harry L. Uy, Theresa Guise, Jose De La Mata, Suzanne D. Taylor, Beryl M. Story, Mark R. Dallas, Brendan F. Boyce, Gregory R. Mundy, G. David Roodman

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Increased production of PTH-related protein (PTHrP) and PTH is frequently responsible for hypercalcemia and its associated morbidity. However, it is unclear whether these peptides produce identical effects on cells in the osteoclast lineage in vivo. To examine the effects of continuous in vivo exposure to these factors on both the osteoclast precursors and mature osteoclasts, we inoculated Chinese hamster ovarian cells expressing PTH-(1- 84), PTHrP-(1-141), or nontransfected Chinese hamster ovarian cells into nude mice. The effects of these tumors on blood ionized calcium, plasma PTH and PTHrP concentrations, and osteoclast formation were then determined. PTH and PTHrP tumor-bearing mice became hypercalcemic (1.90 ± 0.04 and 1.97 ± 0.16 mmol/liter, respectively) compared with control mice (1.29 ± 0.015 mmol/liter). After 4 days of hypercalcemia, mice were killed, and bone marrow cells were harvested to examine cells at three discrete stages of osteoclast development: multipotent osteoclast precursors, the granulocyte/macrophage colony-forming unit; more committed marrow mononuclear osteoclast precursors; and mature osteoclasts. Neither PTH nor PTHrP had an effect on granulocyte/macrophage colony-forming unit, but similarly increased the number of more committed mononuclear osteoclast progenitors as well as mature osteoclasts in the calvaria. No differences were detected between the effects of PTH and PTHrP on cells in the osteoclast lineage in vivo. Thus, PTH and PTHrP appear to affect only more differentiated cells in the osteoclast lineage, and the differences in osteoclastic bone resorption between primary hyperparathyroidism and humoral hypercalcemia of malignancy are probably due to mechanisms other than effects on osteoclast precursor cells in vivo.

Original languageEnglish (US)
Pages (from-to)3207-3212
Number of pages6
JournalEndocrinology
Volume136
Issue number8
DOIs
StatePublished - Aug 1995
Externally publishedYes

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Parathyroid Hormone-Related Protein
Osteoclasts
Parathyroid Hormone
Granulocyte-Macrophage Progenitor Cells
Hypercalcemia
Cricetulus
Primary Hyperparathyroidism
Bone Resorption
Skull
Nude Mice
Bone Marrow Cells
Blood Proteins

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Effects of parathyroid hormone (PTH)-related protein and PTH on osteoclasts and osteoclast precursors in vivo. / Uy, Harry L.; Guise, Theresa; De La Mata, Jose; Taylor, Suzanne D.; Story, Beryl M.; Dallas, Mark R.; Boyce, Brendan F.; Mundy, Gregory R.; Roodman, G. David.

In: Endocrinology, Vol. 136, No. 8, 08.1995, p. 3207-3212.

Research output: Contribution to journalArticle

Uy, HL, Guise, T, De La Mata, J, Taylor, SD, Story, BM, Dallas, MR, Boyce, BF, Mundy, GR & Roodman, GD 1995, 'Effects of parathyroid hormone (PTH)-related protein and PTH on osteoclasts and osteoclast precursors in vivo', Endocrinology, vol. 136, no. 8, pp. 3207-3212. https://doi.org/10.1210/en.136.8.3207
Uy, Harry L. ; Guise, Theresa ; De La Mata, Jose ; Taylor, Suzanne D. ; Story, Beryl M. ; Dallas, Mark R. ; Boyce, Brendan F. ; Mundy, Gregory R. ; Roodman, G. David. / Effects of parathyroid hormone (PTH)-related protein and PTH on osteoclasts and osteoclast precursors in vivo. In: Endocrinology. 1995 ; Vol. 136, No. 8. pp. 3207-3212.
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AB - Increased production of PTH-related protein (PTHrP) and PTH is frequently responsible for hypercalcemia and its associated morbidity. However, it is unclear whether these peptides produce identical effects on cells in the osteoclast lineage in vivo. To examine the effects of continuous in vivo exposure to these factors on both the osteoclast precursors and mature osteoclasts, we inoculated Chinese hamster ovarian cells expressing PTH-(1- 84), PTHrP-(1-141), or nontransfected Chinese hamster ovarian cells into nude mice. The effects of these tumors on blood ionized calcium, plasma PTH and PTHrP concentrations, and osteoclast formation were then determined. PTH and PTHrP tumor-bearing mice became hypercalcemic (1.90 ± 0.04 and 1.97 ± 0.16 mmol/liter, respectively) compared with control mice (1.29 ± 0.015 mmol/liter). After 4 days of hypercalcemia, mice were killed, and bone marrow cells were harvested to examine cells at three discrete stages of osteoclast development: multipotent osteoclast precursors, the granulocyte/macrophage colony-forming unit; more committed marrow mononuclear osteoclast precursors; and mature osteoclasts. Neither PTH nor PTHrP had an effect on granulocyte/macrophage colony-forming unit, but similarly increased the number of more committed mononuclear osteoclast progenitors as well as mature osteoclasts in the calvaria. No differences were detected between the effects of PTH and PTHrP on cells in the osteoclast lineage in vivo. Thus, PTH and PTHrP appear to affect only more differentiated cells in the osteoclast lineage, and the differences in osteoclastic bone resorption between primary hyperparathyroidism and humoral hypercalcemia of malignancy are probably due to mechanisms other than effects on osteoclast precursor cells in vivo.

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