title: Terbium promotes adhesion and osteogenic differentiation of mesenchymal stem cells via activation of the Smad-dependent TGF-β/BMP signaling pathway.
abstract: With its special physical and chemical properties, terbium has been widely used, which has inevitably increased the chance of human exposure to terbium-based compounds. It was reported that terbium mainly deposited in bone after introduction into the human body. Although some studies revealed the effects of terbium on bone cell lines, there have been few reports about the potential effect of terbium on adhesion and differentiation of mesenchymal stem cells (MSCs). In this study, we investigated the effects of terbium on the adhesion and osteogenic and adipogenic differentiation of MSCs and the associated molecular mechanisms. Our data reveal that terbium promoted the osteogenic differentiation in a time-dependent manner and conversely inhibited the adipogenic differentiation of MSCs. Meanwhile, the cell-cell or cell-matrix interaction was enhanced by activating adherent-related key factors, which were evaluated by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Real-time RT-PCR and Western blot analysis were also performed to further detect osteogenic and adipogenic biomarkers of MSCs. The regulation of terbium on differentiation of MSCs led to the interaction between the transforming growth factor β/bone morphogenetic protein and peroxisome-proliferator-activated receptor γ (PPARγ) signaling pathways, resulting in upregulation of the osteogenic master transcription factors, such as Runt-related transcription factor 2, bone morphogenetic protein 2, collagen I, alkaline phosphatase, and osteocalcin, and downregulation of the adipogenic master transcription factors, such as PPARγ2. The results provide novel evidence to elucidate the mechanisms of bone metabolism by terbium and may be helpful for more rational application of terbium-based compounds in the future.
authors.affiliation: College of Chemistry and Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding, 071002, People's Republic of China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Liu
authors.forename: Kun
authors.initials: K
authors.lastname: Ge
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Shu-Xiang
authors.initials: SX
authors.lastname: Wang
authors.forename: Meng-Su
authors.initials: MS
authors.lastname: Yang
authors.forename: Jin-Chao
authors.initials: JC
authors.lastname: Zhang
mesh_terms: D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013725:Terbium / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D047495:PPAR gamma; D016212:Transforming Growth Factor beta; D013725:Terbium