Myeloma cells can directly contribute to the pool of RANKL in bone bypassing the classic stromal and osteoblast pathway of osteoclast stimulation.

Lai, F. P. L.; Cole‐Sinclair, M.; Cheng, W.‐J.; Quinn, J. M. W.; Gillespie, M. T.; Sentry, J. W.; Schneider, H.‐G.

doi:10.1111/j.1365-2141.2004.05018.x

Cited by 86Bone Metabolism and DiseasesMultiple Myeloma Research and TreatmentsBone health and treatments

Myeloma cells can directly contribute to the pool of RANKL in bone bypassing the classic stromal and osteoblast pathway of osteoclast stimulation.

Lai, F. P. L., Cole‐Sinclair, M., Cheng, W.‐J., Quinn, J. M. W., Gillespie, M. T., Sentry, J. W., Schneider, H.‐G.·2004·British Journal of Haematology

DOI 10.1111/j.1365-2141.2004.05018.x

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Abstract

Summary: The ratio of osteoprotegerin [OPG, tumour necrosis factor receptor superfamily, member 11b (TNFRSF11B)] to receptor activator of nuclear factor κB ligand [RANKL, tumour necrosis factor (ligand) superfamily, member 11 (TNFSF11)] in bone is critical for the regulation of bone remodelling. Myeloma cells can home to bone, triggering increased RANKL and decreased OPG expression by stromal cells, leading to osteolysis. Whether myeloma cells contribute directly to the pool of RANKL or OPG in bone has been contentious. Here we provide evidence of RANKL expression by reverse transcription polymerase chain reaction and in situ hybridization, demonstrating transcripts encoding both the membrane‐bound and secreted forms of RANKL in five human multiple myeloma cell lines (LP‐1, NCI‐H929, OPM‐2, RPMI8226, U266) and myeloma cells purified from bone marrow aspirates of myeloma patients. We demonstrated that RANKL encoding mRNAs are translated to protein by antibody detection of RANKL. In vitro assays showed that myeloma cells induced bone marrow derived mononuclear cells to differentiate into adherent tartrate‐resistant acid phosphatase positive multinucleated cells, indicative of the formation of functional osteoclasts. This differentiation could also be achieved with passaged myeloma media alone, implicating secreted products. Finally, we provide evidence that the differentiation observed is at least in part the result of myeloma cell expression of RANKL. We therefore conclude that myeloma cells can directly contribute to the pool of RANKL in bone.

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Prostate cancer cells and multiple myeloma cells express RANKL directly.
“prostate cancer cells (CaP) (314 -316) and MM cells (317-322) have been shown to express RANKL directly.”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [318]

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Authors: Lai, F. P. L., Cole‐Sinclair, M., Cheng, W. ‐., Quinn, J. M. W., Gillespie, M. T., Sentry, J. W., & Schneider, H. ‐.
Affiliations: The Alfred Hospital (AU)
St Vincents Institute of Medical Research (AU)
ORCID: Lai, F. P. L.
Quinn, J. M. W.
Gillespie, M. T.
Schneider, H.‐G.
Venue: British Journal of Haematology
Publisher: Wiley
Published: 2004-06-04
Volume: 126
Issue: 2
Pages: 192-201
ISSN: 0007-1048 (ISSN-L)
1365-2141
DOI: 10.1111/j.1365-2141.2004.05018.x
OpenAlex: W2005360870
Cited by: 86
References: 33
Citations by year: 2026: 2 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 6 · 2013: 4 · 2012: 5
FWCI: 2.37
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: British Journal of Haematology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
Health Sciences › Medicine › Oncology › Bone health and treatments
Keywords: multiple myeloma, RANKL, osteoprotegerin, myeloma cells, osteoclastogenesis, bone remodeling, osteolysis, mesenchymal stem cells, osteoblasts, TNFSF11, myeloma cell lines, bone marrow aspirate
MeSH terms: Tartrate-Resistant Acid Phosphatase, Acid Phosphatase, Carrier Proteins, Cell Differentiation, Cell Division, Humans, Isoenzymes, Leukocytes, Mononuclear, Membrane Glycoproteins, Multiple Myeloma, Osteoclasts, Proteoglycans, RNA, Messenger, Tumor Cells, Cultured, Gene Expression, Culture Media, Conditioned, In Situ Hybridization, Protein Isoforms, Reverse Transcriptase Polymerase Chain Reaction, Cell Line, Tumor, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Syndecans

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Myeloma cells can directly contribute to the pool of RANKL in bone bypassing the classic stromal and osteoblast pathway of osteoclast stimulation.

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