Parathyroid Hormone Stimulates Circulating Osteogenic Cells in Hypoparathyroidism
Open Access
- 1 January 2011
- journal article
- other
- Published by The Endocrine Society in Journal of Clinical Endocrinology & Metabolism
- Vol. 96 (1), 176-186
- https://doi.org/10.1210/jc.2009-2682
Abstract
Context: The osteoanabolic properties of PTH may be due to increases in the number and maturity of circulating osteogenic cells. Hypoparathyroidism is a useful clinical model because this hypothesis can be tested by administering PTH. Objective: The objective of the study was to characterize circulating osteogenic cells in hypoparathyroid subjects during 12 months of PTH (1-84) administration. Design: Osteogenic cells were characterized using flow cytometry and antibodies against osteocalcin, an osteoblast-specific protein product, and stem cell markers CD34 and CD146. Changes in bone formation from biochemical markers and quadruple-labeled transiliac crest bone biopsies (0 and 3 month time points) were correlated with measurements of circulating osteogenic cells. Setting: The study was conducted at a clinical research center. Patients: Nineteen control and 19 hypoparathyroid patients were included in the study. Intervention: Intervention included the administration of PTH (1-84). Results: Osteocalcin-positive cells were lower in hypoparathyroid subjects than controls (0.7 ± 0.1 vs. 2.0 ± 0.1%; P < 0.0001), with greater coexpression of the early cell markers CD34 and CD146 among the osteocalcin-positive cells in the hypoparathyroid subjects (11.0 ± 1.0 vs. 5.6 ± 0.7%; P < 0.001). With PTH (1-84) administration, the number of osteogenic cells increased 3-fold (P < 0.0001), whereas the coexpression of the early cell markers CD34 and CD146 decreased. Increases in osteogenic cells correlated with circulating and histomorphometric indices of osteoblast function: N-terminal propeptide of type I procollagen (R2 = 0.4, P ≤ 0.001), bone-specific alkaline phosphatase (R2 = 0.3, P < 0.001), osteocalcin (R2 = 0.4, P < 0.001), mineralized perimeter (R2 = 0.5, P < 0.001), mineral apposition rate (R2 = 0.4, P = 0.003), and bone formation rate (R2 = 0.5, P < 0.001). Conclusions: It is likely that PTH stimulates bone formation by stimulating osteoblast development and maturation. Correlations between circulating osteogenic cells and histomorphometric indices of bone formation establish that osteoblast activity is being identified by this methodology.Keywords
This publication has 27 references indexed in Scilit:
- Therapy of hypoparathyroidism with intact parathyroid hormoneOsteoporosis International, 2010
- Hematopoietic cells and osteoblasts are derived from a common marrow progenitor after bone marrow transplantationProceedings of the National Academy of Sciences of the United States of America, 2004
- Circulating Skeletal Stem CellsThe Journal of cell biology, 2001
- Birth and Death of Bone Cells: Basic Regulatory Mechanisms and Implications for the Pathogenesis and Treatment of Osteoporosis*Endocrine Reviews, 2000
- Monoclonal antibody assay for measuring bone-specific alkaline phosphatase activity in serumClinical Chemistry, 1995
- Measurement of a more stable region of osteocalcin in serum by ELISA with two monoclonal antibodiesClinical Chemistry, 1995
- Regulation of human bone marrow-derived osteoprogenitor cells by osteogenic growth factors.JCI Insight, 1995
- Expression of human bone-related proteins in the hematopoietic microenvironment.JCI Insight, 1990
- Insulin-like growth factor I mediates selective anabolic effects of parathyroid hormone in bone cultures.JCI Insight, 1989
- Bone histomorphometry: Standardization of nomenclature, symbols, and units: Report of the asbmr histomorphometry nomenclature committeeJournal of Bone and Mineral Research, 1987