Reference - Detail
|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|
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.
|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|
|Human and Animal Cells||MC3T3-E1(RCB1126)|