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Catabolic effects of continuous human PTH (1-38) in vivo is associated with sustained stimulation of RANKL and inhibition of osteoprotegerin and gene-associated bone formation.
Abstract
Continuous infusion of PTH in vivo results in active bone resorption. To investigate the molecular basis of the catabolic effect of PTH in vivo, we evaluated the role of OPG and RANKL, which are known to influence osteoclast formation and function. Weanling rats fed a calcium-free diet were parathyroidectomized and infused with PTH via an Alzet pump to examine: 1) the changes of serum-ionized calcium and osteoclast number, 2) the expression of OPG/RANKL mRNA and protein, and 3) the expression of osteoblast phenotype bone formation-associated genes such as osteoblast specific transcription factor, osteocalcin, bone sialoprotein, and type I collagen. PTH (1–38) (0.01–20 μg/100 g) continuous infusion for 1–24 h resulted in a dose-dependent increase in serum-ionized calcium in parathyroidectomized rats and a corresponding dose-dependent increase in osteoclast number, indicating an increased bone resorption. At 20 μg/100 g PTH dose level, serum-ionized calcium was 2.1-fold of the vehicle control and not different from the Sham-parathyroidectomized rats, and osteoclast number was 3-fold of the vehicle control and 1.7-fold of the Sham-parathyroidectomized rats. In the distal femur, RANKL mRNA expression was increased (27-fold) and OPG mRNA expression was decreased (4.6-fold). The changes in RANKL and OPG mRNA levels were rapid (as early as 1 h), dose dependent, and sustained over a 24-h period that was examined. Immunohistochemical evaluation of bone sections confirmed that OPG level was reduced in proximal tibial metaphysis upon PTH infusion. Circulating OPG protein level was also decreased by 32% when compared with the parathyroidectomized control. The expression of genes that mark the osteoblast phenotype was significantly decreased [osteoblast specific transcription factor (2.3-fold), osteocalcin (3-fold), bone sialoprotein (2.8-fold), and type I collagen (5-fold)]. These results suggest that the catabolic effect of PTH infusion in vivo in this well-established resorption model is associated with a reciprocal expression of OPG/RANKL and a co-ordinate decrease in the expression of bone formation-related genes. We propose that the rapid and sustained increase in RANKL and decrease in OPG initiate maintain and favor the cascade of events in the differentiation/recruitment and activation of osteoclasts.
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“Osteoclast activity is likely to depend, at least in part, on the relative balance of RANKL and OPG.”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [88]
In the citing paper
“PTH infusion led to a dose-dependent increase in RANKL mRNA and a dose-dependent decrease in OPG mRNA (Fig. 4).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [88]
Citations
Cites
Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
Lacey, D. L., Timms, E., Tan, H.-L., Kelley, M. J., Dunstan, C. R., Burgess, T., Elliott, R., Colombero, A., Elliott, G., Scully, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81569-x · Cited by 5,439
PARFITT, A. M., Drezner, M. K., Glorieux, F. H., Kanis, J. А., Malluche, H. H., Meunier, P. J., Ott, S. M., & Recker, R. R. (1987) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650020617 · Cited by 5,344
Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.
Simonet, W. S., Lacey, D. L., Dunstan, C. R., Kelley, M., Chang, M.-S., Lüthy, R., Nguyen, H. Q., Wooden, S., Bennett, L., Boone, T., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80209-3 · Cited by 5,130
Yasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mochizuki, S.-I., Tomoyasu, A., Yano, K., Goto, M., Murakami, A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.3597 · Cited by 4,224
OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph node organogenesis.
Kong, Y.-Y., Yoshida, H., Sarosi, I., Tan, H.-L., Timms, E., Capparelli, C., Morony, S., Oliveira-dos-Santos, A. J., Van, G., Itie, A., et al. (1999) · Nature · doi:10.1038/16852 · Cited by 3,351
Bone Histomorphometry : Standardization of Nomenclature, Symbols, and Units
PARFITT, A. M., Drezner, M. K., Glorieux, F. H., Kanis, J. А., Malluche, H. H., Meunier, P. J., Ott, S. M., & Recker, R. R. (1987) · Journal of Bone and Mineral Research · Cited by 3,258
Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.
Bucay, N., Sarosi, I., Dunstan, C. R., Morony, S., Tarpley, J., Capparelli, C., Scully, S., Tan, H. L., Xu, W., Lacey, D. L., et al. (1998) · Genes & Development · doi:10.1101/gad.12.9.1260 · Cited by 2,483
A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function.
Anderson, D. M., Maraskovsky, E., Billingsley, W. L., Dougall, W. C., Tometsko, M. E., Roux, E. R., Teepe, M. C., DuBose, R. F., Cosman, D., & Galibert, L. (1997) · Nature · doi:10.1038/36593 · Cited by 2,290
Yasuda, H., Shima, N., Nakagawa, N., Mochizuki, S.-I., Yano, K., Fujise, N., Sato, Y., Goto, M., Yamaguchi, K., Kuriyama, M., et al. (1998) · Endocrinology · doi:10.1210/endo.139.3.5837 · Cited by 1,201
Wong, B. R., Rho, J., Arron, J. R., Robinson, E. A., Orlinick, J. R., Chao, M. V., Kalachikov, S. M., Cayani, E., Bartlett, F. S., Frankel, W. N., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.40.25190 · Cited by 1,042
Research works printed but not linked: 2
- Hock, 1994, Anabolic PTH targets proliferating cells of the primary spongiosa in young rats, and increases the number differentiating into osteoblasts, J Bone Miner Res, 9
- Tsukii, 1998, Osteoclast differentiation factor mediates an essential signal for bone resorption induced by 1 alpha,25-dihydroxyvitamin D3, prostaglandin E2, or parathyroid hormone in the microenvironment of bone., Biochem Biophys Res Commun, 246, 337, 10.1006/bbrc.1998.8610 · DOI
Cited by
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Osteoclast differentiation and activation
Boyle, W. J., Simonet, W. S., & Lacey, D. L. (2003) · Nature · doi:10.1038/nature01658 · Cited by 6,670
Cellular and molecular mechanisms of bone remodeling
Raggatt, L. J., & Partridge, N. C. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.r109.041087 · Cited by 1,402
Kearns, A. E., Khosla, S., & Kostenuik, P. J. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0014 · Cited by 824
Endocrine functions of bone in mineral metabolism regulation
Quarles, L. D. (2008) · Journal of Clinical Investigation · doi:10.1172/jci36479 · Cited by 459
Modeling the interactions between osteoblast and osteoclast activities in bone remodeling
Lemaire, V., Tobin, F. L., Greller, L. D., Cho, C. R., & Suva, L. J. (2004) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2004.03.023 · Cited by 452
Metadata
- Authors
- Ma, Y. L., Cain, R. L., Halladay, D. L., Yang, X., Zeng, Q., Miles, R. R., Chandrasekhar, S., Martin, T. J., & Onyia, J. E.
- Affiliations
- Gene Regulation, Bone and Inflammation Research Division (Y.L.M., R.L.C., D.L.H., X.Y., Q.Z., S.C., T.J.M., J.E.O.), Lilly Research Laboratories, Eli Lilly & Co., Indianapolis, Indiana 46285
- Eli Lilly (United States) (US)
- ORCID
- Yang, Xuhao
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2001-09-01
- Volume
- 142
- Issue
- 9
- Pages
- 4047-4054
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2061769753
- Cited by
- 428
- References
- 52
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 7 · 2023: 12 · 2022: 15 · 2021: 12 · 2020: 20 · 2019: 18 · 2018: 18 · 2017: 26 · 2016: 19 · 2015: 14 · 2014: 16 · 2013: 26 · 2012: 23
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Keywords
- parathyroid hormone, bone resorption, RANKL, osteoprotegerin, osteoclasts, osteoblast gene expression, osteocalcin, bone sialoprotein, type I collagen, serum ionized calcium, parathyroidectomy, bone catabolism
- MeSH terms
- Animals, Bone Resorption, Female, Femur, Glycoproteins, Humans, Infusion Pumps, Osteoblasts, Osteogenesis, Parathyroid Hormone, Peptide Fragments, Phenotype, RNA, Messenger, Rats, Sprague-Dawley, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Rats, Osteoprotegerin
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- CoChat. (2026). Citation check: Catabolic effects of continuous human PTH (1-38) in vivo is associated with sustained stimulation of RANKL and inhibition of osteoprotegerin and gene-associated bone formation. https://app.cochat.ai/papers/10.1210/endo.142.9.8356
- The paper
- Ma, Y. L., Cain, R. L., Halladay, D. L., Yang, X., Zeng, Q., Miles, R. R., Chandrasekhar, S., Martin, T. J., & Onyia, J. E. (2001). Catabolic effects of continuous human PTH (1-38) in vivo is associated with sustained stimulation of RANKL and inhibition of osteoprotegerin and gene-associated bone formation. Endocrinology. https://doi.org/10.1210/endo.142.9.8356
