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Cited by 139Bone Metabolism and DiseasesBone health and osteoporosis researchEstrogen and related hormone effects

Effects of dissociated glucocorticoids on OPG and RANKL in osteoblastic cells.

Humphrey, E.L., Williams, J.H.H., Davie, M.W.J., Marshall, M.J.·2006·Bone
DOI 10.1016/j.bone.2005.10.004
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Abstract

Glucocorticoids are effective anti-inflammatory and immunosuppressive agents, but their use is often associated with debilitating side effects such as glucocorticoid-induced osteoporosis. Newly developed glucocorticoid analogues such as the so-called dissociated glucocorticoids are potent immunosuppressants and have the potential for fewer side effects. The effects of these new analogues on osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) in osteoblastic cells have not been studied. OPG and RANKL are osteoblast-derived proteins pivotal to the regulation of bone mass. RANKL stimulates bone resorption by increasing osteoclast differentiation, activation and survival. OPG is the decoy receptor for RANKL and thus inhibits bone resorption. Here, we show that dexamethasone, prednisolone, deflazacort and the dissociated glucocorticoids, RU24858, RU40066, RU24782, AL438-F1 and ZK216348 significantly inhibit OPG production in two human osteoblastic cell lines (MG63 and hFOB). The potency for OPG inhibition was ligand and cell-type specific. In both cell types, dexamethasone and prednisolone were the most potent ligands inhibiting OPG production with IC(50)s of approximately 0.1 nM and 10 nM respectively. In MG63 cells, deflazacort and the RU compounds were the next most potent ligands followed by AL438-F1 and ZK216348. In hFOB cells, however, the RU compounds were the least potent ligands with an IC(50) 74 times higher than in MG63 cells. In contrast, the level of maximum inhibition or effectiveness of OPG inhibition did not vary between cell types but did vary according to the ligand. Dexamethasone, prednisolone, deflazacort and the RU compounds all inhibited OPG production by a maximum of approximately 70-80%, whereas AL438-F1 and ZK 216348 inhibited OPG production by a maximum of only 40-50% at 1 microM. All of the dissociated glucocorticoids and deflazacort were poor stimulators of RANKL gene expression stimulating by only approximately 1-3-fold compared to 7-fold by prednisolone. These data demonstrate that deflazacort and the dissociated glucocorticoids are weak stimulators of the RANKL:OPG ratio compared to prednisolone. Therefore, these compounds have the potential to cause less bone loss than that seen with prednisolone, though this was not investigated here.

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Authors
Humphrey, E. L., Williams, J. H. H., Davie, M. W. J., & Marshall, M. J.
Affiliations
  • Robert Jones and Agnes Hunt Orthopaedic Hospital (GB)
  • University of Chester (GB)
Corresponding author
Marshall, M.J.
ORCID
Venue
Bone
Publisher
Elsevier BV
Published
2006-05
Volume
38
Issue
5
Pages
652-661
ISSN
  • 1873-2763 (ISSN-L)
  • 8756-3282
DOI
10.1016/j.bone.2005.10.004
OpenAlex
W2034541958
Cited by
139
References
57
Citations by year
2026: 4 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 10 · 2021: 10 · 2020: 5 · 2019: 6 · 2018: 7 · 2017: 2 · 2016: 9 · 2015: 8 · 2014: 3 · 2013: 8 · 2012: 9
FWCI
3.53
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Bone (publishedVersion)
  • PubMed (publishedVersion)
  • ChesterRep (University of Chester) (submittedVersion)
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
osteoprotegerin, RANKL, osteoblasts, glucocorticoid-induced osteoporosis, bone resorption, deflazacort, dexamethasone, prednisolone, MG-63 cells, RANK signaling
MeSH terms
Carrier Proteins, Desoximetasone, Dexamethasone, Glucocorticoids, Glycoproteins, Humans, Hydroxycorticosteroids, Membrane Glycoproteins, Osteoblasts, Prednisolone, Pregnenediones, Gene Expression, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B

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