- Author
- Arne Martens (UGent) , Pieter Hertens (UGent) , Dario Priem (UGent) , Vagelis Rinotas, Theodore Meletakos, Meropi Gennadi, Lisette Van Hove, Els Louagie (UGent) , Julie Coudenys (UGent) , Amélie De Muynck, Djoere Gaublomme (UGent) , Mozes Sze (UGent) , Jolanda van Hengel (UGent) , Leen Catrysse (UGent) , Esther Hoste (UGent) , Jeffrey D. Zajac, Rachel A. Davey, Luc Van Hoorebeke (UGent) , Tino Hochepied (UGent) , Mathieu Bertrand (UGent) , Marietta Armaka, Dirk Elewaut (UGent) and Geert van Loo (UGent)
- Organization
- Project
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- Investigating the molecular mechanisms and therapeutic use of A20 and MYSM1 in inflammatory signaling and pathology
- Investigating itaconic acid as a critical immunometabolite in Influenza and RSV infections
- Study of microbiota-host interactions during colon cancer development using a unique microbiome dependent mouse model
- Host-microbe interaction in intestinal homeostasis: unravelling the mechanisms involved in the onset of multiple inflammation-related diseases
- Study of the molecular pathways through which linear (de)ubiquitination governs skin inflammation and aberrant epidermal stem cell activation
- UGCT – Ghent University Centre for X-ray Tomography
- Abstract
- The anti-inflammatory protein A20 serves as a critical brake on NF-kappa B signaling and NF-kappa B-dependent inflammation. In humans, polymorphisms in or near the TNFAIP3/A20 gene have been associated with several inflammatory disorders, including rheumatoid arthritis (RA), and experimental studies in mice have demonstrated that myeloid-specific A20 deficiency causes the development of a severe polyarthritis resembling human RA. Myeloid A20 deficiency also promotes osteoclastogenesis in mice, suggesting a role for A20 in the regulation of osteoclast differentiation and bone formation. We show here that osteoclast-specific A20 knockout mice develop severe osteoporosis, but not inflammatory arthritis. In vitro, osteoclast precursor cells from A20 deficient mice are hyper-responsive to RANKL-induced osteoclastogenesis. Mechanistically, we show that A20 is recruited to the RANK receptor complex within minutes of ligand binding, where it restrains NF-kappa B activation independently of its deubiquitinating activity but through its zinc finger (ZnF) 4 and 7 ubiquitin-binding functions. Together, these data demonstrate that A20 acts as a regulator of RANK-induced NF-kappa B signaling to control osteoclast differentiation, assuring proper bone development and turnover.
- Keywords
- osteoporosis, inflammation, osteoclast, bone, A20
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01GP3N4FKM3QHFYCR35P6XCBR0
- MLA
- Martens, Arne, et al. “A20 Controls RANK-Dependent Osteoclast Formation and Bone Physiology.” EMBO REPORTS, vol. 23, no. 12, 2022, doi:10.15252/embr.202255233.
- APA
- Martens, A., Hertens, P., Priem, D., Rinotas, V., Meletakos, T., Gennadi, M., … van Loo, G. (2022). A20 controls RANK-dependent osteoclast formation and bone physiology. EMBO REPORTS, 23(12). https://doi.org/10.15252/embr.202255233
- Chicago author-date
- Martens, Arne, Pieter Hertens, Dario Priem, Vagelis Rinotas, Theodore Meletakos, Meropi Gennadi, Lisette Van Hove, et al. 2022. “A20 Controls RANK-Dependent Osteoclast Formation and Bone Physiology.” EMBO REPORTS 23 (12). https://doi.org/10.15252/embr.202255233.
- Chicago author-date (all authors)
- Martens, Arne, Pieter Hertens, Dario Priem, Vagelis Rinotas, Theodore Meletakos, Meropi Gennadi, Lisette Van Hove, Els Louagie, Julie Coudenys, Amélie De Muynck, Djoere Gaublomme, Mozes Sze, Jolanda van Hengel, Leen Catrysse, Esther Hoste, Jeffrey D. Zajac, Rachel A. Davey, Luc Van Hoorebeke, Tino Hochepied, Mathieu Bertrand, Marietta Armaka, Dirk Elewaut, and Geert van Loo. 2022. “A20 Controls RANK-Dependent Osteoclast Formation and Bone Physiology.” EMBO REPORTS 23 (12). doi:10.15252/embr.202255233.
- Vancouver
- 1.Martens A, Hertens P, Priem D, Rinotas V, Meletakos T, Gennadi M, et al. A20 controls RANK-dependent osteoclast formation and bone physiology. EMBO REPORTS. 2022;23(12).
- IEEE
- [1]A. Martens et al., “A20 controls RANK-dependent osteoclast formation and bone physiology,” EMBO REPORTS, vol. 23, no. 12, 2022.
@article{01GP3N4FKM3QHFYCR35P6XCBR0,
abstract = {{The anti-inflammatory protein A20 serves as a critical brake on NF-kappa B signaling and NF-kappa B-dependent inflammation. In humans, polymorphisms in or near the TNFAIP3/A20 gene have been associated with several inflammatory disorders, including rheumatoid arthritis (RA), and experimental studies in mice have demonstrated that myeloid-specific A20 deficiency causes the development of a severe polyarthritis resembling human RA. Myeloid A20 deficiency also promotes osteoclastogenesis in mice, suggesting a role for A20 in the regulation of osteoclast differentiation and bone formation. We show here that osteoclast-specific A20 knockout mice develop severe osteoporosis, but not inflammatory arthritis. In vitro, osteoclast precursor cells from A20 deficient mice are hyper-responsive to RANKL-induced osteoclastogenesis. Mechanistically, we show that A20 is recruited to the RANK receptor complex within minutes of ligand binding, where it restrains NF-kappa B activation independently of its deubiquitinating activity but through its zinc finger (ZnF) 4 and 7 ubiquitin-binding functions. Together, these data demonstrate that A20 acts as a regulator of RANK-induced NF-kappa B signaling to control osteoclast differentiation, assuring proper bone development and turnover.}},
articleno = {{e55233}},
author = {{Martens, Arne and Hertens, Pieter and Priem, Dario and Rinotas, Vagelis and Meletakos, Theodore and Gennadi, Meropi and Van Hove, Lisette and Louagie, Els and Coudenys, Julie and De Muynck, Amélie and Gaublomme, Djoere and Sze, Mozes and van Hengel, Jolanda and Catrysse, Leen and Hoste, Esther and Zajac, Jeffrey D. and Davey, Rachel A. and Van Hoorebeke, Luc and Hochepied, Tino and Bertrand, Mathieu and Armaka, Marietta and Elewaut, Dirk and van Loo, Geert}},
issn = {{1469-221X}},
journal = {{EMBO REPORTS}},
keywords = {{osteoporosis,inflammation,osteoclast,bone,A20}},
language = {{eng}},
number = {{12}},
pages = {{12}},
title = {{A20 controls RANK-dependent osteoclast formation and bone physiology}},
url = {{http://doi.org/10.15252/embr.202255233}},
volume = {{23}},
year = {{2022}},
}
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