Intermittent parathyroid hormone administration converts quiescent lining cells to active osteoblasts
Open accessAbstract
Intermittent administration of parathyroid hormone (PTH) increases bone mass, at least in part, by increasing the number of osteoblasts. One possible source of osteoblasts might be conversion of inactive lining cells to osteoblasts, and indirect evidence is consistent with this hypothesis. To better understand the possible effect of PTH on lining cell activation, a lineage tracing study was conducted using an inducible gene system. Dmp1-CreERt2 mice were crossed with ROSA26R reporter mice to render targeted mature osteoblasts and their descendents, lining cells and osteocytes, detectable by 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside (X-gal) staining. Dmp1-CreERt2(+):ROSA26R mice were injected with 0.25 mg 4-OH-tamoxifen (4-OHTam) on postnatal days 3, 5, 7, 14, and 21. The animals were euthanized on postnatal day 23, 33, or 43 (2, 12, or 22 days after the last 4-OHTam injection). On day 43, mice were challenged with a subcutaneous injection of human PTH (1–34, 80 µg/kg) or vehicle once daily for 3 days. By 22 days after the last 4-OHTam injection, most X-gal (+) cells on the periosteal surfaces of the calvaria and the tibia were flat. Moreover, bone formation rate and collagen I(α1) mRNA expression were decreased at day 43 compared to day 23. After 3 days of PTH injections, the thickness of X-gal (+) cells increased, as did their expression of osteocalcin and collagen I(α1) mRNA. Electron microscopy revealed X-gal–associated chromogen particles in thin cells prior to PTH administration and in cuboidal cells following PTH administration. These data support the hypothesis that intermittent PTH treatment can increase osteoblast number by converting lining cells to mature osteoblasts in vivo. © 2012 American Society for Bone and Mineral Research.
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BLCs can react to PTH exposure by quickly reverting to osteoblasts and thus expand the osteoblastic pool to fill resorption lacunae.
“For example, BLCs can react to PTH exposure by quickly reverting to osteoblasts and thus expand the osteoblastic pool258 to fill resorption lacunae, similar to process in the “anabolic window” after teriparatide and abaloparatide administration.259”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [258]
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- Authors
- Kim, S. W., Pajevic, P. D., Selig, M., Barry, K. J., Yang, J.-Y., Shin, C. S., Baek, W.-Y., Kim, J.-E., & Kronenberg, H. M.
- Affiliations
- Harvard University (US)
- Seoul National University (KR)
- Kyungpook National University (KR)
- Corresponding author
- Kronenberg, Henry M
- ORCID
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-05-23
- Volume
- 27
- Issue
- 10
- Pages
- 2075-2084
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- PMC
- PMC3529414
- OpenAlex
- W2065308524
- Cited by
- 266
- References
- 23
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 16 · 2023: 14 · 2022: 18 · 2021: 23 · 2020: 32 · 2019: 37 · 2018: 15 · 2017: 19 · 2016: 17 · 2015: 25 · 2014: 20 · 2013: 10 · 2012: 4
- FWCI
- 7.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R56DK079161, DK11794, P01DK011794, R01DK079161, DK079161)
- 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, intermittent PTH administration, osteogenic differentiation, osteoblast lineage, lineage tracing, bone formation, type I collagen, osteocalcin, periosteum, bone mass
- MeSH terms
- Animals, beta-Galactosidase, Bromodeoxyuridine, Humans, Mice, Inbred C57BL, Osteoblasts, Osteogenesis, Parathyroid Hormone, Periosteum, Skull, Tibia, Cell Lineage, Cell Proliferation, Mice
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