Cited by 114Bone Metabolism and DiseasesBone health and osteoporosis researchOsteomyelitis and Bone Disorders Research

The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.

Local Production of Osteoprotegerin by Osteoblasts Suppresses Bone Resorption

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Abstract

Osteoprotegerin (OPG) inhibits the ability of receptor activator of nuclear factor κB (NF-κB) ligand (RANKL) to stimulate the differentiation, activity, and survival of bone-resorbing osteoclasts. Genetic studies in mice show that osteocytes are an important source of RANKL, but the cellular sources of OPG are unclear. We use conditional deletion of Tnfrsf11b, which encodes OPG, from different cell populations to identify functionally relevant sources of OPG in mice. Deletion from B lymphocytes and osteocytes, two cell types commonly thought to supply OPG, has little or no impact on bone mass. By contrast, deletion of Tnfrsf11b from osteoblasts increases bone resorption and reduces bone mass to an extent similar to germline deletion, demonstrating that osteoblasts are an essential source of OPG. These results suggest that, in addition to producing new bone matrix, osteoblasts also play an active role in terminating the resorption phase of the bone remodeling cycle by suppressing RANKL activity.

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Metadata

Authors
Cawley, K. M., Bustamante-Gomez, N. C., Guha, A. G., MacLeod, R. S., Xiong, J., Gubrij, I., Liu, Y., Mulkey, R., Palmieri, M., Thostenson, J. D., Goellner, J. J., & O’Brien, C. A.
Affiliations
  • University of Arkansas for Medical Sciences (US)
  • Central Arkansas Veterans Healthcare System (US)
Corresponding author
O’Brien, Charles A.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2020-09
Volume
32
Issue
10
Pages
108052
ISSN
2211-1247 (ISSN-L)
OpenAlex
W3084164734
Cited by
114
References
49
Citations by year
2026: 15 · 2025: 18 · 2024: 15 · 2023: 20 · 2022: 28 · 2021: 13 · 2020: 5
FWCI
5.35
Type
journal article
Language
en
Update notices
erratum (2025-06-24)
Open access
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
Funders
  • U.S. Department of Veterans Affairs (I01 BX000294)
  • University of Arkansas for Medical Sciences
  • National Institutes of Health (R01AR049794, P20GM125503)
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 › Rheumatology › Osteomyelitis and Bone Disorders Research
Keywords
osteoprotegerin, osteoblasts, bone resorption, RANKL, osteocytes, B cells, bone remodeling, conditional gene deletion, bone mass, osteoclasts
MeSH terms
Animals, Cell Differentiation, Humans, Osteoblasts, Osteoclasts, Osteocytes, Bone Remodeling, Mice, Osteoprotegerin

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