Local Production of Osteoprotegerin by Osteoblasts Suppresses Bone Resorption
Open accessAbstract
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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T cells signal to B cells to induce OPG expression.
“Furthermore, T cells signal to B cells to induce OPG expression [76, 77].”
From Osteoimmunology of Fracture Healing. (2024) · cites this paper as [76]
The Introduction and Discussion state that B cells produce OPG. They do not say that T cells signal to B cells or induce that production; the paper’s B-cell deletion experiment addresses OPG’s role in bone resorption, not how its expression is induced. (LLM, conf=0.83)
Experimental — accuracy not yet measuredOPG released by mature osteoblasts and/or osteocytes may constitute the termination signal of the resorption phase in the remodeling cycle.
“Nevertheless, OPG released by mature osteoblasts and/or osteocytes may constitute the termination signal of the resorption phase in the remodeling cycle.77”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [77]
OPG inhibitory activity is mandatory for the correct shift from bone resorption to bone formation and protects newly formed bone against untimely resorption.
“This inhibitory activity is mandatory for the correct shift from bone resorption to bone formation and protects newly formed bone against untimely resorption.77”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [77]
The local concentration of OPG near the cell surface is a key factor in its ability to block the activity of RANKL.
“Cawley’s study stressed the concept “that the local concentration of OPG near the cell surface is a key factor in its ability to block the activity of RANKL”.”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [77]
Osteocytes can be considered dynamic cells capable of reconstituted mechanical sensitivity after replacement and inhibitory control over osteoclastogenesis via local production of OPG.
“Hence, osteocytes can be considered dynamic cells capable of reconstituted mechanical sensitivity after replacement293 as well as the inhibitory control over osteoclastogenesis via the local production of OPG.77”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [77]
As osteoblasts mature, they secrete more ECM and exert local inhibitory control over osteoclastogenesis by releasing OPG.
“Moreover, as cells mature, they secrete more ECM and exert local inhibitory control over osteoclastogenesis by releasing the osteoclastogenic inhibitor OPG.77”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [77]
Osteoblasts are major sources of OPG in cancellous bone, acting with osteocytes and other cells to modulate the RANKL/RANK ratio and reduce resorption by osteoclasts.
“Osteoblasts are considered the major sources of OPG in cancellous bone, acting in concert with osteocytes and other cells to modulate the RANKL/RANK ratio and reduce resorption by osteoclasts.”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [77]
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- 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.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 32
- Issue
- 10
- Pages
- 108052
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC7493998
- 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
- gold
- doi.org
- Licence
- 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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