title: Factors circulating in the blood of type 2 diabetes mellitus patients affect osteoblast maturation - description of a novel in vitro model.
abstract: Type 2 diabetes mellitus (T2DM) is one of the most frequent metabolic disorders in industrialized countries. Among other complications, T2DM patients have an increased fracture risk and delayed fracture healing. We have demonstrated that supraphysiological glucose and insulin levels inhibit primary human osteoblasts׳ maturation. We aimed at developing a more physiologically relevant in vitro model to analyze T2DM-mediated osteoblast changes. Therefore, SCP-1-immortalized pre-osteoblasts were differentiated with T2DM or control (non-obese and obese) sera. Between both control groups, no significant changes were observed. Proliferation was significantly increased (1.69-fold), while AP activity and matrix mineralization was significantly reduced in the T2DM group. Expression levels of osteogenic marker genes and transcription factors were altered, e.g. down-regulation of RUNX2 and SP-7 or up-regulation of STAT1, in the T2DM group. Active TGF-β levels were significantly increased (1.46-fold) in T2DM patients׳ sera. SCP-1 cells treated with these sera showed significantly increased TGF-β signaling (2.47-fold). Signaling inhibition effectively restored osteoblast maturation in the T2DM group. Summarizing our data, SCP-1 cells differentiated in the presence of T2DM patients׳ serum exhibit reduced osteoblast function. Thus, this model has a high physiological impact, as it can identify circulating factors in T2DM patients׳ blood that may affect bone function, e.g. TGF-β.
authors.affiliation: BG Trauma Center, Eberhard Karls Universität Tübingen, Schnarrenbergstr. 95, D-72076 Tübingen, Germany. Electronic address: sabrina.ehnert@gmail.com.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Ehnert
authors.affiliation: BG Trauma Center, Eberhard Karls Universität Tübingen, Schnarrenbergstr. 95, D-72076 Tübingen, Germany. Electronic address: tfreude@bgu-tuebingen.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Freude
authors.affiliation: BG Trauma Center, Eberhard Karls Universität Tübingen, Schnarrenbergstr. 95, D-72076 Tübingen, Germany. Electronic address: cihle@bgu-tuebingen.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Ihle
authors.affiliation: BG Trauma Center, Eberhard Karls Universität Tübingen, Schnarrenbergstr. 95, D-72076 Tübingen, Germany. Electronic address: lara.nk@gmail.com.
authors.forename: Larissa
authors.initials: L
authors.lastname: Mayer
authors.affiliation: BG Trauma Center, Eberhard Karls Universität Tübingen, Schnarrenbergstr. 95, D-72076 Tübingen, Germany. Electronic address: bianca.braun@med.uni-tuebingen.de.
authors.forename: Bianca
authors.initials: B
authors.lastname: Braun
authors.affiliation: BG Trauma Center, Eberhard Karls Universität Tübingen, Schnarrenbergstr. 95, D-72076 Tübingen, Germany. Electronic address: jessica.graeser@student.reutlingen-university.de.
authors.forename: Jessica
authors.initials: J
authors.lastname: Graeser
authors.affiliation: BG Trauma Center, Eberhard Karls Universität Tübingen, Schnarrenbergstr. 95, D-72076 Tübingen, Germany. Electronic address: iflesch@bgu-tuebingen.de.
authors.forename: Ingo
authors.initials: I
authors.lastname: Flesch
authors.affiliation: BG Trauma Center, Eberhard Karls Universität Tübingen, Schnarrenbergstr. 95, D-72076 Tübingen, Germany. Electronic address: ustoeckle@bgu-tuebingen.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Stöckle
authors.affiliation: BG Trauma Center, Eberhard Karls Universität Tübingen, Schnarrenbergstr. 95, D-72076 Tübingen, Germany. Electronic address: andreas.nuessler@gmail.com.
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Nussler
authors.affiliation: Department of Diabetology, Klinikum Traunstein, Kliniken Südostbayern AG, Cuno-Niggl-Str. 3, D-83278 Traunstein, Germany. Electronic address: stefan.pscherer@t-online.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Pscherer
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D001851:Bone Diseases, Metabolic / Q000097:blood* / Q000209:etiology; D016022:Case-Control Studies; D002454:Cell Differentiation; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000097:blood*
chemical_list: D016212:Transforming Growth Factor beta; D000469:Alkaline Phosphatase
keywords: Diabetes mellitus type 2; Osteogenesis; SCP-1 cells; Transforming growth factor beta