An anti-inflammatory selective glucocorticoid receptor modulator preserves osteoblast differentiation
(2011) FASEB JOURNAL. 25(4). p.1323-1332- abstract
- Glucocorticoids (GCs) are in widespread use to treat inflammatory bone diseases, such as rheumatoid arthritis (RA). Their anti-inflammatory efficacy, however, is accompanied by deleterious effects on bone, leading to GC-induced osteoporosis (GIO). These effects include up-regulation of the receptor activator of NF-kappa B ligand/osteoprotegerin (RANKL/OPG) ratio to promote bone-resorbing osteoclasts and include inhibition of bone-forming osteoblasts. We previously identified suppression of osteoblast differentiation by the monomer glucocorticoid receptor (GR) via the inhibition of Il11 expression as a crucial mechanism for GIO. Here we show that the GR-modulating substance compound A (CpdA), which does not induce GR dimerization, still suppresses proinflammatory cytokines in fibroblast-like synovial cells from patients with RA and in osteoblasts. In contrast to the full GR agonist dexamethasone, it does not unfavorably alter the RANKL/OPG ratio and does not affect Il11 expression and subsequent STAT3 phosphorylation in these cells. Notably, while dexamethasone inhibits osteoblast differentiation, CpdA does not affect osteoblast differentiation in vitro and in vivo. We describe here for the first time that selective GR modulators can act against inflammation, while not impairing osteoblast differentiation.
Please use this url to cite or link to this publication:
http://hdl.handle.net/1854/LU-1890324
- author
- Alexander Rauch, Valerie Gossye UGent, Debby Bracke UGent, Elien Gevaert UGent, Peggy Jacques UGent, Katrien Van Beneden UGent, BERNARD VANDOOREN UGent, Martina Rauner, Lorenz C Hofbauer, Guy Haegeman, Dirk Elewaut UGent, Jan P Tuckermann and Karolien De Bosscher UGent
- organization
- year
- 2011
- type
- journalArticle (original)
- publication status
- published
- subject
- keyword
- RHEUMATOID-ARTHRITIS, SUPPRESS BONE-FORMATION, OSTEOCLAST DIFFERENTIATION, SYNOVIAL FIBROBLASTS, GENE REPRESSION, PLANT-ORIGIN, CATHEPSIN-K, MECHANISMS, CELLS, GR, osteoporosis, interleukin 11, FACTOR-KAPPA-B
- journal title
- FASEB JOURNAL
- Faseb J.
- volume
- 25
- issue
- 4
- pages
- 1323 - 1332
- Web of Science type
- Article
- Web of Science id
- 000288982800021
- JCR category
- BIOLOGY
- JCR impact factor
- 5.712 (2011)
- JCR rank
- 7/84 (2011)
- JCR quartile
- 1 (2011)
- ISSN
- 0892-6638
- DOI
- 10.1096/fj.10-173393
- project
- Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
- language
- English
- UGent publication?
- yes
- classification
- A1
- copyright statement
- I have transferred the copyright for this publication to the publisher
- id
- 1890324
- handle
- http://hdl.handle.net/1854/LU-1890324
- date created
- 2011-08-18 15:57:31
- date last changed
- 2016-12-19 15:39:11
@article{1890324, abstract = {Glucocorticoids (GCs) are in widespread use to treat inflammatory bone diseases, such as rheumatoid arthritis (RA). Their anti-inflammatory efficacy, however, is accompanied by deleterious effects on bone, leading to GC-induced osteoporosis (GIO). These effects include up-regulation of the receptor activator of NF-kappa B ligand/osteoprotegerin (RANKL/OPG) ratio to promote bone-resorbing osteoclasts and include inhibition of bone-forming osteoblasts. We previously identified suppression of osteoblast differentiation by the monomer glucocorticoid receptor (GR) via the inhibition of Il11 expression as a crucial mechanism for GIO. Here we show that the GR-modulating substance compound A (CpdA), which does not induce GR dimerization, still suppresses proinflammatory cytokines in fibroblast-like synovial cells from patients with RA and in osteoblasts. In contrast to the full GR agonist dexamethasone, it does not unfavorably alter the RANKL/OPG ratio and does not affect Il11 expression and subsequent STAT3 phosphorylation in these cells. Notably, while dexamethasone inhibits osteoblast differentiation, CpdA does not affect osteoblast differentiation in vitro and in vivo. We describe here for the first time that selective GR modulators can act against inflammation, while not impairing osteoblast differentiation.}, author = {Rauch, Alexander and Gossye, Valerie and Bracke, Debby and Gevaert, Elien and Jacques, Peggy and Van Beneden, Katrien and VANDOOREN, BERNARD and Rauner, Martina and Hofbauer, Lorenz C and Haegeman, Guy and Elewaut, Dirk and Tuckermann, Jan P and De Bosscher, Karolien}, issn = {0892-6638}, journal = {FASEB JOURNAL}, keyword = {RHEUMATOID-ARTHRITIS,SUPPRESS BONE-FORMATION,OSTEOCLAST DIFFERENTIATION,SYNOVIAL FIBROBLASTS,GENE REPRESSION,PLANT-ORIGIN,CATHEPSIN-K,MECHANISMS,CELLS,GR,osteoporosis,interleukin 11,FACTOR-KAPPA-B}, language = {eng}, number = {4}, pages = {1323--1332}, title = {An anti-inflammatory selective glucocorticoid receptor modulator preserves osteoblast differentiation}, url = {http://dx.doi.org/10.1096/fj.10-173393}, volume = {25}, year = {2011}, }
- Chicago
- Rauch, Alexander, Valerie Gossye, Debby Bracke, Elien Gevaert, Peggy Jacques, Katrien Van Beneden, BERNARD VANDOOREN, et al. 2011. “An Anti-inflammatory Selective Glucocorticoid Receptor Modulator Preserves Osteoblast Differentiation.” Faseb Journal 25 (4): 1323–1332.
- APA
- Rauch, A., Gossye, V., Bracke, D., Gevaert, E., Jacques, P., Van Beneden, K., VANDOOREN, B., et al. (2011). An anti-inflammatory selective glucocorticoid receptor modulator preserves osteoblast differentiation. FASEB JOURNAL, 25(4), 1323–1332.
- Vancouver
- 1.Rauch A, Gossye V, Bracke D, Gevaert E, Jacques P, Van Beneden K, et al. An anti-inflammatory selective glucocorticoid receptor modulator preserves osteoblast differentiation. FASEB JOURNAL. 2011;25(4):1323–32.
- MLA
- Rauch, Alexander, Valerie Gossye, Debby Bracke, et al. “An Anti-inflammatory Selective Glucocorticoid Receptor Modulator Preserves Osteoblast Differentiation.” FASEB JOURNAL 25.4 (2011): 1323–1332. Print.