system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Adipocytes, Adiponectin, Aged, Aged, 80 and over, Bone Marrow Cells, Cells, Cultured, Dexamethasone, Enzyme-Linked Immunosorbent Assay, Female, Femur Neck, Gene Expression Regulation, Glucocorticoids, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Male, Middle Aged, Plasminogen Activator Inhibitor 1, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Simvastatin, Time Factors.
user
Does simvastatin suppress dexamethasone-induced secretion of plasminogen activator inhibitor-1 in human bone marrow adipocytes? Context: Osteonecrosis of the femoral head is a common complication of high-dose glucocorticoid treatment. Intravascular thrombosis is thought to be associated with the ischemic state of the femoral head. Plasminogen activator inhibitor-1 (PAI-1) is an adipokine, which are physiologically active substances secreted from visceral and subcutaneous adipocytes. PAI-1 suppresses fibrinolysis by binding tissue-type plasminogen activator. Several reports have described the relationship between PAI-1 and steroid-induced osteonecrosis of the femoral head, and the preventive effects of lipid-lowering agents (statins) against steroid-induced osteonecrosis of the femoral head. We previously reported that adipokines and dexamethasone induced PAI-1 secretion from bone marrow adipocytes. The purpose of the present study is to examine the effects of simvastatin on PAI-1 secretion from human bone marrow adipocytes in vitro. Primary bone marrow adipocytes were extracted from collagenase-treated bone marrow fluid obtained from the femoral necks of 40 patients (6 men, 34 women; age range, 52-81 years) undergoing hip joint replacement surgery. After suspended culture with or without dexamethasone or simvastatin, PAI-1 mRNA expression was assessed by real-time RT-PCR. Total PAI-1 protein secretion in culture medium was assessed by enzyme-linked immunosorbent assay. PAI-1 mRNA expression was up-regulated by 388% (P=0.002) with dexamethasone, and down-regulated by 45% (P=0.002) with simvastatin, as compared to control levels. Dexamethasone increased total PAI-1 secretion by 166% (P=0.001) and simvastatin decreased total PAI-1 secretion by 64% (P=0.002). No significant changes were observed in adiponectin mRNA expression and secretion by dexamethasone and simvastatin, while pre-treatment with simvastatin reversed dexamethasone induced PAI-1 secretion by 89%, as compared to control levels.
assistant
The present study confirmed the suppressive effects of simvastatin on PAI-1 expression and secretion from bone marrow adipocytes. Furthermore, pre-treatment with simvastatin reversed dexamethasone induced PAI-1 secretion. Simvastatin may thus exhibit preventive effects against steroid-induced osteonecrosis of the femoral head by suppressing PAI-1 secretion. Final Decision: yes