Ethanol may suppress Wnt/beta-catenin signaling on human bone marrow stroma cells: a preliminary study.
Ethanol and glucocorticoids are risk factors associated with osteonecrosis. Previous reports suggest ethanol and glucocorticoids induce adipogenesis, decrease osteogenesis in bone marrow stroma cells, and produce intracellular lipid deposits resulting in death of osteocytes. The Wnt/beta-catenin signal pathway is involved in the regulation of homeostasis of bone and we presume glucocorticoids and ethanol may induce osteonecrosis in humans through a similar mechanism as in rodents. We hypothesized (1) ethanol, like glucocorticoids, decreases osteogenesis and increases adipogenesis through the Wnt/beta-catenin signaling pathway in human bone marrow stromal cells; and (2) ethanol decreases intranuclear translocation of beta-catenin. We found both dexamethasone and ethanol decrease the gene and protein expression of osteogenesis and increase that of adipogenesis through Wnt signaling-related genes by semiquantitative and quantitative polymerase chain reaction and Western blot. Ethanol hampered intranuclear translocation of beta-catenin by immunofluorescence analysis. The data suggest the Wnt/beta-catenin signaling pathway may be associated with ethanol-induced osteonecrosis.
Yeh
Ching-Hua
CH
Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chang
Je-Ken
JK
Wang
Yan-Hsiung
YH
Ho
Mei-Ling
ML
Wang
Gwo-Jaw
GJ
D021581:Active Transport, Cell Nucleus; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D000305:Adrenal Cortex Hormones / Q000633:toxicity; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D000431:Ethanol / Q000633:toxicity*; D006801:Humans; D008856:Microscopy, Fluorescence; D039902:Multipotent Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D010020:Osteonecrosis / Q000139:chemically induced / Q000378:metabolism; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D000305:Adrenal Cortex Hormones; C495270:CTNNB1 protein, human; D012333:RNA, Messenger; D051153:Wnt Proteins; D051176:beta Catenin; D000431:Ethanol; D003907:Dexamethasone