Cargando…

Glucocorticoids employ the monomeric glucocorticoid receptor to potentiate vitamin D(3) and parathyroid hormone–induced osteoclastogenesis

Glucocorticoid (GC) therapy decreases bone mass and increases the risk of fractures. We investigated interactions between the GC dexamethasone (DEX) and the bone resorptive agents 1,25(OH)(2)-vitamin D(3) (D3) and parathyroid hormone (PTH) on osteoclastogenesis. We observed a synergistic potentiatio...

Descripción completa

Detalles Bibliográficos
Autores principales: Conaway, H. Herschel, Henning, Petra, Lie, Antia, Tuckermann, Jan, Lerner, Ulf H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Federation of American Societies for Experimental Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894088/
https://www.ncbi.nlm.nih.gov/pubmed/31675485
http://dx.doi.org/10.1096/fj.201802729RRR
_version_ 1783476321455702016
author Conaway, H. Herschel
Henning, Petra
Lie, Antia
Tuckermann, Jan
Lerner, Ulf H.
author_facet Conaway, H. Herschel
Henning, Petra
Lie, Antia
Tuckermann, Jan
Lerner, Ulf H.
author_sort Conaway, H. Herschel
collection PubMed
description Glucocorticoid (GC) therapy decreases bone mass and increases the risk of fractures. We investigated interactions between the GC dexamethasone (DEX) and the bone resorptive agents 1,25(OH)(2)-vitamin D(3) (D3) and parathyroid hormone (PTH) on osteoclastogenesis. We observed a synergistic potentiation of osteoclast progenitor cell differentiation and formation of osteoclasts when DEX was added to either D3- or PTH-treated mouse bone marrow cell (BMC) cultures. Cotreatment of DEX with D3 or PTH increased gene encoding calcitonin receptor (Calcr), acid phosphatase 5, tartrate resistant (Acp5), cathepsin K (Ctsk), and TNF superfamily member 11 (Tnfsf11) mRNA, receptor activator of NF-κB ligand protein (RANKL), numbers of osteoclasts on plastic, and pit formation and release of C-terminal fragment of type I collagen from cells cultured on bone slices. Enhanced RANKL protein expression caused by D3 and DEX was absent in BMC from mice in which the GC receptor (GR) was deleted in stromal cells/osteoblasts. Synergistic interactions between DEX and D3 on RANKL and osteoclast formation were present in BMC from mice with attenuated GR dimerization. These data demonstrate that the GR cooperates with D3 and PTH signaling, causing massive osteoclastogenesis, which may explain the rapid bone loss observed with high dosages of GC treatment.—Conaway, H. H., Henning, P., Lie, A., Tuckermann, J., Lerner, U. H. Glucocorticoids employ the monomeric glucocorticoid receptor to potentiate vitamin D(3) and parathyroid hormone–induced osteoclastogenesis.
format Online
Article
Text
id pubmed-6894088
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Federation of American Societies for Experimental Biology
record_format MEDLINE/PubMed
spelling pubmed-68940882019-12-10 Glucocorticoids employ the monomeric glucocorticoid receptor to potentiate vitamin D(3) and parathyroid hormone–induced osteoclastogenesis Conaway, H. Herschel Henning, Petra Lie, Antia Tuckermann, Jan Lerner, Ulf H. FASEB J Research Glucocorticoid (GC) therapy decreases bone mass and increases the risk of fractures. We investigated interactions between the GC dexamethasone (DEX) and the bone resorptive agents 1,25(OH)(2)-vitamin D(3) (D3) and parathyroid hormone (PTH) on osteoclastogenesis. We observed a synergistic potentiation of osteoclast progenitor cell differentiation and formation of osteoclasts when DEX was added to either D3- or PTH-treated mouse bone marrow cell (BMC) cultures. Cotreatment of DEX with D3 or PTH increased gene encoding calcitonin receptor (Calcr), acid phosphatase 5, tartrate resistant (Acp5), cathepsin K (Ctsk), and TNF superfamily member 11 (Tnfsf11) mRNA, receptor activator of NF-κB ligand protein (RANKL), numbers of osteoclasts on plastic, and pit formation and release of C-terminal fragment of type I collagen from cells cultured on bone slices. Enhanced RANKL protein expression caused by D3 and DEX was absent in BMC from mice in which the GC receptor (GR) was deleted in stromal cells/osteoblasts. Synergistic interactions between DEX and D3 on RANKL and osteoclast formation were present in BMC from mice with attenuated GR dimerization. These data demonstrate that the GR cooperates with D3 and PTH signaling, causing massive osteoclastogenesis, which may explain the rapid bone loss observed with high dosages of GC treatment.—Conaway, H. H., Henning, P., Lie, A., Tuckermann, J., Lerner, U. H. Glucocorticoids employ the monomeric glucocorticoid receptor to potentiate vitamin D(3) and parathyroid hormone–induced osteoclastogenesis. Federation of American Societies for Experimental Biology 2019-12 2019-11-14 /pmc/articles/PMC6894088/ /pubmed/31675485 http://dx.doi.org/10.1096/fj.201802729RRR Text en © The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Conaway, H. Herschel
Henning, Petra
Lie, Antia
Tuckermann, Jan
Lerner, Ulf H.
Glucocorticoids employ the monomeric glucocorticoid receptor to potentiate vitamin D(3) and parathyroid hormone–induced osteoclastogenesis
title Glucocorticoids employ the monomeric glucocorticoid receptor to potentiate vitamin D(3) and parathyroid hormone–induced osteoclastogenesis
title_full Glucocorticoids employ the monomeric glucocorticoid receptor to potentiate vitamin D(3) and parathyroid hormone–induced osteoclastogenesis
title_fullStr Glucocorticoids employ the monomeric glucocorticoid receptor to potentiate vitamin D(3) and parathyroid hormone–induced osteoclastogenesis
title_full_unstemmed Glucocorticoids employ the monomeric glucocorticoid receptor to potentiate vitamin D(3) and parathyroid hormone–induced osteoclastogenesis
title_short Glucocorticoids employ the monomeric glucocorticoid receptor to potentiate vitamin D(3) and parathyroid hormone–induced osteoclastogenesis
title_sort glucocorticoids employ the monomeric glucocorticoid receptor to potentiate vitamin d(3) and parathyroid hormone–induced osteoclastogenesis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894088/
https://www.ncbi.nlm.nih.gov/pubmed/31675485
http://dx.doi.org/10.1096/fj.201802729RRR
work_keys_str_mv AT conawayhherschel glucocorticoidsemploythemonomericglucocorticoidreceptortopotentiatevitamind3andparathyroidhormoneinducedosteoclastogenesis
AT henningpetra glucocorticoidsemploythemonomericglucocorticoidreceptortopotentiatevitamind3andparathyroidhormoneinducedosteoclastogenesis
AT lieantia glucocorticoidsemploythemonomericglucocorticoidreceptortopotentiatevitamind3andparathyroidhormoneinducedosteoclastogenesis
AT tuckermannjan glucocorticoidsemploythemonomericglucocorticoidreceptortopotentiatevitamind3andparathyroidhormoneinducedosteoclastogenesis
AT lernerulfh glucocorticoidsemploythemonomericglucocorticoidreceptortopotentiatevitamind3andparathyroidhormoneinducedosteoclastogenesis