Effects of iguratimod on glucocorticoid-induced disorder of bone metabolism in vitro.
Alkaline Phosphatase
/ genetics
Animals
Arthritis, Rheumatoid
/ drug therapy
Bone Marrow Cells
/ drug effects
Bone Resorption
/ pathology
Bone and Bones
/ drug effects
Calcification, Physiologic
/ drug effects
Cell Count
Cell Line
Chromones
/ pharmacology
Dexamethasone
Down-Regulation
/ drug effects
Glucocorticoids
/ adverse effects
Male
Mice, Inbred C57BL
Osteoblasts
/ drug effects
Osteoclasts
/ drug effects
Osteogenesis
/ drug effects
Sulfonamides
/ pharmacology
Up-Regulation
/ drug effects
Glucocorticoid-induced osteoporosis
Iguratimod
Osteoblast
Osteoclast
Osteocyte
Journal
Journal of bone and mineral metabolism
ISSN: 1435-5604
Titre abrégé: J Bone Miner Metab
Pays: Japan
ID NLM: 9436705
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
19
12
2020
accepted:
08
01
2021
pubmed:
11
2
2021
medline:
23
7
2021
entrez:
10
2
2021
Statut:
ppublish
Résumé
Glucocorticoids are widely used to treat various diseases including rheumatoid arthritis (RA); however, one of the most frequent and severe adverse effects is glucocorticoid-induced osteoporosis (GIOP). Iguratimod (IGU) is a novel conventional synthetic disease-modifying anti-rheumatic drug developed in Japan. The aim of this study is to investigate the effects of IGU on glucocorticoid-induced disorder of bone metabolism in vitro. In osteoclastogenesis of mouse bone marrow-derived cells, tartrate-resistant acid phosphatase staining, resorption pit assay, western blotting, real-time polymerase chain reaction (PCR), and mRNA sequencing were performed. In osteoblastogenesis of MC3T3-E1 cells, alkaline phosphatase (ALP) staining and activity, alizarin red staining, and mRNA sequencing were performed, and real-time PCR and western blotting were conducted in MC3T3-E1 cells and murine osteocyte-like cell line MLO-Y4 cells. IGU significantly suppressed a dexamethasone-induced increase in osteoclasts, differentiation, and bone resorption activity by inhibition of the receptor activator of the nuclear factor kappa-B (RANK)/tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)/nuclear factor kappa-B (NFκB)-p52 pathway. In MC3T3-E1 cells, IGU significantly upregulated dexamethasone-induced downregulation of ALP activity, bone mineralization, and osteoblast-related gene and protein expression. In MLO-Y4 cells, IGU significantly upregulated dexamethasone-induced downregulation of the gene expression of ALP and osteocalcin, and also downregulated receptor activator of NFκB ligand (RANKL)/osteoprotegerin gene expression ratio without dexamethasone. These results suggest that IGU may improve glucocorticoid-induced disorder of bone metabolism and may exhibit positive effects against GIOP associated with RA.
Identifiants
pubmed: 33564917
doi: 10.1007/s00774-021-01206-5
pii: 10.1007/s00774-021-01206-5
doi:
Substances chimiques
Chromones
0
Glucocorticoids
0
Sulfonamides
0
iguratimod
4IHY34Y2NV
Dexamethasone
7S5I7G3JQL
Alkaline Phosphatase
EC 3.1.3.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
639-648Références
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