title: Biphasic influence of hypoxia on tuftelin expression in mouse mesenchymal C3H10T1/2 stem cells.
abstract: Tuftelin, an acidic protein, thought to play a role in the initial stages of ectodermal enamel mineralization, has since been detected in mesenchymal-derived tissues. During bone/cartilage development and regeneration, mesenchymal stem cells (MSCs) undergo an avascular period in a hypoxic environment, involving induction of hypoxia-inducible factor 1-alpha (HIF-1-alpha), a key component in this process. In the present study we investigated, in a mouse mesenchymal C3H10T1/2 stem cell model, the hypothesis that oxygen stress modulates tuftelin 1 expression in relation to HIF-1-alpha (Hif1a), in a mouse mesenchymal C3H10T1/2 stem cell model. The results of the present study showed a biphasic induction of tuftelin, similar to the pattern of HIF-1-alpha expression, in MSCs subjected to a hypoxic insult of 1% O(2) through a period of 2-24 h. Immunocytochemistry analysis of the cells exposed to hypoxic insult for 2-24 h revealed the same biphasic pattern of tuftelin protein expression. Tuftelin localization appears to be mainly in the cytoplasm, and concentrated at the perinuclear region of the cells by 24 h of hypoxic insult. Based on our previous studies using the neuronal PC12 cell model, in which tuftelin induction was mediated by Hif1a, we propose that tuftelin is a member of oxygen-sensitive genes and implicated in the adaptive mechanisms regulating MSC function.
authors.affiliation: Dental Research Laboratory, Institute of Dental Sciences, Faculty of Dental Medicine, The Hebrew University of Jerusalem - Hadassah, Jerusalem, Israel. dddan@cc.huji.ac.il
authors.forename: Dan
authors.initials: D
authors.lastname: Deutsch
authors.forename: Nechama
authors.initials: N
authors.lastname: Silverstein
authors.forename: Dekel
authors.initials: D
authors.lastname: Shilo
authors.forename: Shimon
authors.initials: S
authors.lastname: Lecht
authors.forename: Philip
authors.initials: P
authors.lastname: Lazarovici
authors.forename: Anat
authors.initials: A
authors.lastname: Blumenfeld
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D016923:Cell Death; D015687:Cell Hypoxia / Q000502:physiology*; D002478:Cells, Cultured; D003746:Dental Enamel Proteins / Q000096:biosynthesis* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H
chemical_list: D003746:Dental Enamel Proteins; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C038456:tuftelin; D007770:L-Lactate Dehydrogenase