Enhanced RANK ligand expression and responsivity of bone marrow cells in Paget’s disease of bone.
Open accessAbstract
Paget's disease is characterized by highly localized areas of increased osteoclast (OCL) activity. This suggests that the microenvironment in pagetic lesions is highly osteoclastogenic, or that OCL precursors in these lesions are hyperresponsive to osteoclastogenic factors (or both). To examine these possibilities, we compared RANK ligand (RANKL) mRNA expression in a marrow stromal cell line developed from a pagetic lesion (PSV10) with that in a normal stromal cell line (Saka), and expression in marrow samples from affected bones of Paget's patients with that in normal marrow. RANKL mRNA was increased in PSV10 cells and pagetic marrow compared with Saka cells and normal marrow, and was also increased in marrow from affected bones compared with uninvolved bones from Paget's patients. Furthermore, pagetic marrow cells formed OCLs at much lower RANKL concentrations than did normal marrow. Anti-IL-6 decreased the RANKL responsivity of pagetic marrow to normal levels, whereas addition of IL-6 to normal marrow enhanced RANKL responsivity. Thus, RANKL expression and responsivity is increased in pagetic lesions, in part mediated by IL-6. These data suggest that the combination of enhanced expression of RANKL in affected bones and increased RANKL sensitivity of pagetic OCL precursors may contribute to the elevated numbers of OCLs in Paget's disease.
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RANKL expression is abundant in cultures of stromal or marrow cells from pagetic bone compared with nonaffected bone from the same individuals.
“RANKL expression is abundant in cultures of stromal cells or marrow cells derived from pagetic bone compared with nonaffected bone of the same individuals (394, 395).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [394]
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- Authors
- Menaa, C., Reddy, S. V., Kurihara, N., Maeda, H., Anderson, D., Cundy, T., Cornish, J., Singer, F. R., Bruder, J. M., & Roodman, G. D.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Amgen (United States) (US)
- University of Auckland (NZ)
- United States Department of Veterans Affairs (US)
- Corresponding author
- Roodman, G. David
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2000-06-15
- Volume
- 105
- Issue
- 12
- Pages
- 1833-1838
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC378510
- OpenAlex
- W2132675666
- Cited by
- 154
- References
- 23
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 1 · 2020: 5 · 2019: 8 · 2018: 5 · 2017: 4 · 2016: 5 · 2015: 2 · 2014: 3 · 2013: 6 · 2012: 10
- FWCI
- 3.14
- 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
- National Institute on Aging (R01AG013625)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-44603, AR41336, R01AR044603, R01AR041336)
- National Institute of Dental and Craniofacial Research (DE 12603, R01DE012603)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Keywords
- Paget's disease of bone, RANK ligand, osteoclastogenesis, osteoclast precursors, mesenchymal stem cells, interleukin-6, osteoclast activity, bone microenvironment
- MeSH terms
- Interleukin-6 Inhibitors, Antibodies, Bone and Bones, Bone Marrow Cells, Carrier Proteins, Cells, Cultured, Gene Expression Regulation, Humans, Membrane Glycoproteins, Osteitis Deformans, Osteoclasts, Reference Values, RNA, Messenger, Transcription, Genetic, Interleukin-6, Stromal Cells, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B
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