MLO-Y4 Osteocyte-Like Cells Support Osteoclast Formation and Activation
Open accessAbstract
Osteocytes are terminally differentiated cells of the osteoblast lineage that have become embedded in mineralized matrix and may send signals that regulate bone modeling and remodeling. The hypothesis to be tested in this study is that osteocytes can stimulate and support osteoclast formation and activation. To test this hypothesis, an osteocyte-like cell line called MLO-Y4 and primary murine osteocytes were used in coculture with spleen or marrow cells. MLO-Y4 cells support osteoclast formation in the absence of 1,25-dihydroxyvitamin D3 [1,25(OD)2D3] or any other exogenous osteotropic factor. These cells alone stimulate osteoclast formation to the same extent or greater than adding 1,25(OH)2D3. Coaddition of 1,25(OH)2D3 with MLO-Y4 cells synergistically increased osteoclast formation. Optimal osteoclast formation and pit formation on dentine was observed with 200–1000 MLO-Y4 cells per 0.75-cm2 well. No osteoclast formation was observed with 2T3, OCT-1, or MC3T3-E1 osteoblast cells (1000 cells/well). Conditioned media from the MLO-Y4 cells had no effect on osteoclast formation, indicating that cell contact is necessary. Serial digestions of 2-week-old mouse calvaria yielded populations of cells that support osteoclast formation when cocultured with 1,25(OH)2D3 and marrow, but the population that remained in the bone particles supported the greatest number of osteoclasts with or without 1,25(OH)2D3. To examine the mechanism whereby these cells support osteoclast formation, the MLO-Y4 cells were compared with a series of osteoblast and stromal cells for expression of macrophage colony-stimulating factor (M-CSF), RANKL, and osteoprotegerin (OPG). MLO-Y4 cells express and secrete large amounts of M-CSF. MLO-Y4 cells express RANKL on their surface and their dendritic processes. The ratio of RANKL to OPG mRNA is greatest in the MLO-Y4 cells compared with the other cell types. RANK-Fc and OPG-Fc blocked the formation of osteoclasts by MLO-Y4 cells. These studies suggest that both RANKL and OPG may play a role in osteocyte signaling, OPG and M-CSF as soluble factors and RANKL as a surface molecule that is functional in osteocytes or along their exposed dendritic processes.
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MLO-Y4 cells and primary murine osteocytes cocultured with bone marrow precursors supported osteoclastogenesis, but their conditioned media alone did not, suggesting that cell-cell interactions between osteocytes and osteoclasts are needed for osteoclastogenesis.
“MLO-Y4 cells and primary murine osteocytes cocultured with bone marrow precursors supported osteoclastogenesis, but their conditioned media alone did not have a similar effect,55 suggesting that cell–cell interactions between osteocytes and osteoclasts are needed for osteoclastogenesis.”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [55]
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- Authors
- Zhao, S., Kato, Y., Zhang, Y., Harris, S., Ahuja, S. S., & Bonewald, L. F.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Asahi Kasei (Japan) (JP)
- Corresponding author
- Bonewald, L. F.
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-11-01
- Volume
- 17
- Issue
- 11
- Pages
- 2068-2079
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W2032474228
- Cited by
- 322
- References
- 56
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 9 · 2023: 14 · 2022: 10 · 2021: 14 · 2020: 20 · 2019: 19 · 2018: 13 · 2017: 15 · 2016: 12 · 2015: 18 · 2014: 27 · 2013: 19 · 2012: 21
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (7r01ar042372-08)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-42372, P01AR046798, AR 46798)
- 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 › Bone and Dental Protein Studies
- Keywords
- osteocytes, osteoclastogenesis, osteoclast activation, MLO-Y4 cells, RANKL, osteoprotegerin, macrophage colony-stimulating factor, 1,25-dihydroxyvitamin D3, bone remodeling, bone resorption
- MeSH terms
- Animals, Bone Marrow Cells, Calcitriol, Carrier Proteins, Cell Differentiation, Cells, Cultured, Glycoproteins, Membrane Glycoproteins, Osteoclasts, Osteocytes, Skull, Surface Properties, Macrophage Colony-Stimulating Factor, Culture Media, Conditioned, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Coculture Techniques, Mice, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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