Parathyroid hormone stimulates bone formation and resorption in organ culture: evidence for a coupling mechanism.
Open accessAbstract
We have developed an in vitro system, using embryonic chicken tibiae grown in a serum-free medium, which exhibits simultaneous bone formation and resorption. Tibiae from 8-day embryos increased in mean (+/- SD) length (4.0 +/- 0.4 to 11.0 +/- 0.3 mm) and dry weight (0.30 +/- 0.04 to 0.84 +/- 0.04 mg) during 12 days in vitro. There was increased incorporation of [3H]proline into hydroxyproline (120 +/- 20 to 340 +/- 20 cpm/mg of bone per 24 hr) as a measure of collagen synthesis, as well as a 62 +/- 5% increase in total calcium and 45Ca taken up as an indication of active mineralization. A physiologic concentration (1 pM) of parathyroid hormone was found to stimulate bone resorption over control levels in this system. Parathyroid hormone stimulated the release of [3H]hydroxyproline from the bone shafts but not from the cartilage ends, indicating the specificity of the response. With 1 pM parathyroid hormone we observed an acute inhibition of bone formation, followed (after 12-16 hr) by a chronic stimulation of bone formation during the 12-day incubation. Both mineral uptake and matrix formation were enhanced at approximately the same rate during the 12-day incubation. The chronic enhancement of formation required parathyroid hormone only for the initial 8-10 hr of incubation. These results could be explained by the production or release of a factor from bone to stimulate formation in response to the acute increase in resorption--a "coupling factor." Indeed, dialyzed culture medium conditioned by actively resorbing bones stimulated bone formation over controls when added to organ cultures at a 1:20 dilution. The factor is larger than 12,000 daltons as determined by dialysis. The factor is specific for the bone shaft and did not affect the cartilage ends.
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During bone remodeling, direct and indirect communications among bone cells (coupling mechanism) include soluble coupling factors stored in bone matrix that are released after osteoclast bone resorption.
“It is known that during bone remodeling cycle, there are direct and indirect communications among bone cells in a process called coupling mechanism, which include soluble coupling factors stored in bone matrix that would be released after osteoclast bone resorption [169].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [169]
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- Authors
- Howard, G. A., Bottemiller, B. L., Turner, R. T., Rader, J. I., & Baylink, D. J.
- Affiliations
- United States Department of Veterans Affairs (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1981-05
- Volume
- 78
- Issue
- 5
- Pages
- 3204-3208
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC319529
- OpenAlex
- W2019545214
- Cited by
- 266
- References
- 24
- Citations by year
- 2026: 5 · 2024: 1 · 2023: 1 · 2022: 7 · 2021: 5 · 2020: 11 · 2019: 6 · 2018: 4 · 2017: 7 · 2016: 2 · 2015: 8 · 2014: 5 · 2013: 6 · 2012: 4
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- 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 › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
- Keywords
- parathyroid hormone, bone formation, bone resorption, coupling coefficient, mineralization, collagen synthesis, calcium uptake, bone matrix, conditioned medium, cartilage
- MeSH terms
- Animals, Bone and Bones, Bone Resorption, Calcium, Cartilage, Chick Embryo, Hydroxyproline, Kinetics, Organ Culture Techniques, Parathyroid Hormone, Proline
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