Transforming Growth Factor β Affects Osteoclast Differentiation via Direct and Indirect Actions
Abstract
Transforming growth factor beta (TGF-beta) is abundant in bone and has complex effects on osteolysis, with both positive and negative effects on osteoclast differentiation, suggesting that it acts via more than one mechanism. Osteoclastogenesis is determined primarily by osteoblast (OB) expression of the tumor necrosis factor (TNF)-related molecule receptor activator of NF-kappaB ligand (RANKL) and its decoy receptor osteoprotegerin (OPG), which are increased and decreased, respectively, by osteolytic factors. A RANKL-independent osteoclastogenic mechanism mediated by TNF-alpha has also been shown. Therefore, we investigated TGF-beta effects on osteoclast formation in culture systems in which osteoclastogenic stimulus is dependent on OBs and culture systems where it was provided by exogenously added RANKL or TNF-alpha. Both OPG and TGF-beta inhibited osteoclast formation in hemopoietic cell/OB cocultures, but the kinetics of their action differed. TGF-beta also inhibited osteoclastogenesis in cocultures of cells derived from OPG null (opg-/-) mice. TGF-beta strongly decreased RANKL messenger RNA (mRNA) expression in cultured osteoblasts, and addition of exogenous RANKL to TGFbeta-inhibited cocultures of opg-/- cells partially restored osteoclastogenesis. Combined, these data indicate that the inhibitory actions of TGF-beta were mediated mainly by decreased OB production of RANKL. In contrast, in the absence of OBs, TGF-beta greatly increased osteoclast formation in recombinan…
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TGF-β, released from the bone matrix during bone resorption, enhances osteoclast differentiation in RANKL- and M-CSF-stimulated HSC cultures.
“Transforming growth factor-β, which is released from the bone matrix during bone resorption, has been shown to enhance osteoclast differentiation in RANKL- and M-CSF-stimulated HSC cultures [35].”
From Osteoclasts and Microgravity (2020) · cites this paper as [35]
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“(35) suggests that osteoclasto genic response to TNFa depends on prior exposure of cells to low levels of RANKL (including before extraction of cells from tissue of origin), which is difficult to assess or to control for.”
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- Authors
- Quinn, J. M. W., Itoh, K., Udagawa, N., Häusler, K., Yasuda, H., Shima, N., Mizuno, A., Higashio, K., Takahashi, N., Suda, T., Martin, T. J., & Gillespie, M. T.
- Affiliations
- The University of Melbourne (AU)
- SHOWA Medical University (JP)
- Department of Medicine, St. Vincent's Institute of Medical Research and The University of Melbourne, Fitzroy, Victoria, Australia
- Megmilk Snow Brand (Japan) (JP)
- Corresponding author
- Quinn, Julian M. W.
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-10-01
- Volume
- 16
- Issue
- 10
- Pages
- 1787-1794
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W2065784567
- Cited by
- 278
- References
- 3
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 9 · 2023: 7 · 2022: 9 · 2021: 11 · 2020: 14 · 2019: 13 · 2018: 4 · 2017: 13 · 2016: 7 · 2015: 12 · 2014: 15 · 2013: 10 · 2012: 8
- FWCI
- 4.31
- Type
- journal article
- Language
- en
- Open access
- closed
- 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)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- TGF-beta, osteoclastogenesis, RANKL, osteoprotegerin, TNF-α, osteoblasts, osteolysis, osteoclast precursors, bone remodeling
- MeSH terms
- Animals, Carrier Proteins, Cell Differentiation, Cells, Cultured, Glycoproteins, Membrane Glycoproteins, Mice, Inbred C57BL, Osteoclasts, Spleen, Tumor Necrosis Factor-alpha, Transforming Growth Factor beta, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Coculture Techniques, Mice, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B
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