Activated parathyroid hormone/parathyroid hormone–related protein receptor in osteoblastic cells differentially affects cortical and trabecular bone
Open accessAbstract
Parathyroid hormone (PTH), an important regulator of calcium homeostasis, targets most of its complex actions in bone to cells of the osteoblast lineage. Furthermore, PTH is known to stimulate osteoclastogenesis indirectly through activation of osteoblastic cells. To assess the role of the PTH/PTH-related protein receptor (PPR) in mediating the diverse actions of PTH on bone in vivo, we generated mice that express, in cells of the osteoblastic lineage, one of the constitutively active receptors described in Jansen's metaphyseal chondrodysplasia. In these transgenic mice, osteoblastic function was increased in the trabecular and endosteal compartments, whereas it was decreased in the periosteum. In trabecular bone of the transgenic mice, there was an increase in osteoblast precursors, as well as in mature osteoblasts. Osteoblastic expression of the constitutively active PPR induced a dramatic increase in osteoclast number in both trabecular and compact bone in transgenic animals. The net effect of these actions was a substantial increase in trabecular bone volume and a decrease in cortical bone thickness of the long bones. These findings, for the first time to our knowledge, identify the PPR as a crucial mediator of both bone-forming and bone-resorbing actions of PTH, and they underline the complexity and heterogeneity of the osteoblast population and/or their regulatory microenvironment.
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The systemic factors important to the maintenance of bone homeostasis include parathyroid hormone (PTH), calcitonin, 1,25-dihydroxyvitamin D3 (calcitriol), glucocorticoids, androgens, and estrogens.
“The systemic factors which are important to the maintenance of bone homeostasis include parathyroid hormone (PTH), calcitonin, 1,25-dihydroxyvitamin D3 (calcitriol), glucocorticoids, androgens, and estrogens [16, 147–150].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [147]
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- Authors
- Calvi, L. M., Sims, N. A., Hunzelman, J. L., Knight, M. C., Giovannetti, A., Saxton, J. M., Kronenberg, H. M., Baron, R., & Schipani, E.
- Affiliations
- Harvard University (US)
- Yale University (US)
- Corresponding author
- Schipani, E.
- Venue
- Journal of Clinical Investigation
- Published
- 2001-02-01
- Volume
- 107
- Issue
- 3
- Pages
- 277-286
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC199196
- OpenAlex
- W2135087298
- Cited by
- 388
- References
- 31
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 7 · 2023: 13 · 2022: 10 · 2021: 12 · 2020: 17 · 2019: 16 · 2018: 12 · 2017: 21 · 2016: 11 · 2015: 13 · 2014: 15 · 2013: 12 · 2012: 21
- FWCI
- 6.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ar045354-03)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK07028, F32DK060317, T32DK007028)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-44855, P50AR044855, AR-45354)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- parathyroid hormone, osteoblasts, constitutively active receptor, trabecular bone, cortical bone, osteoclastogenesis, bone resorption, bone formation, osteoblast precursors, periosteum, transgenic mice, bone volume
- MeSH terms
- Age Factors, Animals, Bone and Bones, Mice, Transgenic, Mutation, Osteoblasts, Parathyroid Hormone, Tibia, Signal Transduction, Bone Remodeling, In Situ Hybridization, Receptors, Parathyroid Hormone, Receptor, Parathyroid Hormone, Type 1, Mice
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