RRC ID 63712
Author Miyama A, Ebina K, Hirao M, Okamura G, Etani Y, Takami K, Goshima A, Miura T, Oyama S, Kanamoto T, Yoshikawa H, Nakata K.
Title Effects of iguratimod on glucocorticoid-induced disorder of bone metabolism in vitro.
Journal J Bone Miner Metab
Abstract INTRODUCTION: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.
MATERIALS AND METHODS: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.
RESULTS: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.
CONCLUSION:These results suggest that IGU may improve glucocorticoid-induced disorder of bone metabolism and may exhibit positive effects against GIOP associated with RA.
Volume 39(4)
Pages 639-648
Published 2021-7-1
DOI 10.1007/s00774-021-01206-5
PII 10.1007/s00774-021-01206-5
PMID 33564917
MeSH Alkaline Phosphatase / genetics Alkaline Phosphatase / metabolism Animals Arthritis, Rheumatoid / drug therapy Bone Marrow Cells / drug effects Bone Marrow Cells / pathology Bone Resorption / pathology Bone and Bones / drug effects Bone and Bones / metabolism* Bone and Bones / pathology* Calcification, Physiologic / drug effects Cell Count Cell Line Chromones / pharmacology Chromones / therapeutic use* Dexamethasone Down-Regulation / drug effects Glucocorticoids / adverse effects* Male Mice, Inbred C57BL Osteoblasts / drug effects Osteoblasts / metabolism Osteoclasts / drug effects Osteoclasts / metabolism Osteoclasts / pathology Osteogenesis / drug effects Sulfonamides / pharmacology Sulfonamides / therapeutic use* Up-Regulation / drug effects
IF 2.297
Human and Animal Cells MC3T3-E1(RCB1126)