title: Dexamethasone-induced plasminogen activator inhibitor-1 expression in human primary bone marrow adipocytes.
abstract: Several studies have demonstrated the association of plasminogen activator inhibitor-1 (PAI-1) with osteonecrosis, but the underlying mechanism of osteonecrosis and its relationship with local PAI-1 is not clear. The objective of this study was to evaluate PAI-1 production by primary human bone marrow adipocytes and the effects of glucocorticoid administration. Bone marrow was obtained from 25 individuals during prosthetic insertion. Mature adipocytes were cultured for 24 h with or without dexamethasone. PAI-1, adiponectin, tumor necrosing factor-α (TNFα) expression were measured by latex photometric immunoassay or RT-PCR. Adiponectin, TNFα and PAI-1 were detected in all culture media. PAI-1 expression was significantly increased by treatment with 10(-6) mol/L dexamethasone up to 24 h in protein and mRNA levels, while the levels of other adipokines did not change by dexamethasone. These results suggest that bone marrow adipocytes may play important roles for the development of glucocorticoid-induced osteonecrotic diseases by enhancing PAI-1 expression.
authors.affiliation: Departement of Orthopaedic Surgery, Graduate School of Biomedical Science, Nagasaki University, Nagasaki, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hozumi
authors.forename: Makoto
authors.initials: M
authors.lastname: Osaki
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Hisataka
authors.initials: H
authors.lastname: Goto
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fukushima
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shindo
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000009:adverse effects / Q000494:pharmacology*; D005271:Femur Head Necrosis / Q000209:etiology; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D005938:Glucocorticoids; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C051321:SERPINE1 protein, human; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone