title: Steroid sulfatase in the human MG-63 preosteoblastic cell line: Antagonistic regulation by glucocorticoids and NFκB.
abstract: Steroid sulfatase (STS) converts sulfated steroids into active forms in cells. Preosteoblastic cells possess STS, but its role and regulation in bone are unclear. We examined STS activity and gene expression during differentiation of human MG-63 preosteoblasts. STS activity and gene expression were decreased during differentiation in cells treated with osteogenic supplement containing dexamethasone (DEX). DEX also inhibited STS activity and expression in undifferentiated cells, and the glucocorticoid antagonist RU486 reversed DEX inhibition of STS. These data may have implications for glucocorticoid-induced osteoporosis. The NFκB activators lipopolysaccharide and phorbol myristate acetate increased STS expression in undifferentiated and differentiated MG-63 cells, while the NFκB inhibitor BAY-11-7082 partially blocked these responses. The antagonistic actions of glucocorticoids and NFkB on STS expression are similar to the regulation of inflammatory response proteins. We propose a model of STS regulation whereby inflammation leads to increased STS, resulting in increased estrogen, which modulates the inflammatory response.
authors.affiliation: Department of Biological Sciences, Duquesne University, Pittsburgh, PA, USA.
authors.forename: Natasha J
authors.initials: NJ
authors.lastname: Dias
authors.affiliation: Department of Biological Sciences, Duquesne University, Pittsburgh, PA, USA. Electronic address: selcer@duq.edu.
authors.forename: Kyle W
authors.initials: KW
authors.lastname: Selcer
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D043266:Steryl-Sulfatase / Q000235:genetics / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009570:Nitriles; D012333:RNA, Messenger; D013450:Sulfones; D015735:Mifepristone; D003907:Dexamethasone; D000469:Alkaline Phosphatase; D043266:Steryl-Sulfatase; D013755:Tetradecanoylphorbol Acetate
keywords: Bone; Dexamethasone; Differentiation; Glucocorticoid; Inflammation; NFκB; Osteoblast; Regulation; Steroid sulfatase