title: The dual-effects of LaCl₃ on the proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells.
abstract: A series of experimental methods including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, alkaline phosphatase (ALP) activity measurement, alizarin red S stain and measurement, quantitative real-time reverse transcriptase polymerase chain reaction, and Western blot analysis were employed to assess the effects of LaCl₃ on the proliferation, osteogenic differentiation, and mineralization of a murine preosteoblast cell line MC3T3-E1 at cell and molecular levels. The results indicated that LaCl₃ had dual effects on the proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells. First, LaCl₃ promoted the proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells at lower concentrations, then had no effects and further turned to inhibit the proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells with increasing concentrations. The expression of runt-related transcription factor 2 (Runx2), bone morphogenetic protein 2 (BMP2), ALP, bone sialoprotein (BSP), collagen I (Col I), and osteocalcin (OCN) genes was upregulated in the presence of 0.0001 and 0.1 μM LaCl₃, but these genes were downregulated in the MC3T3-E1 cells treated with 1,000 μM LaCl₃. In addition, the expression of BMP2, Runx2, and OCN proteins was promoted by LaCl₃ at the concentration of 0.0001 μM, but these proteins were downregulated after 1,000 μM LaCl₃ treatment. The results suggest that LaCl₃ likely up- or downregulates the expression of Runx2, which subsequently up- or downregulates osteoblasts marker genes Col I and BMP2 at early stages and ALP and OCN at later stages of differentiation, thus causes to promote or inhibit the proliferation, osteogenic differentiation and mineralization of MC3T3-E1 cells. The results will be helpful for understanding the mechanisms of bone metabolism and application of lanthanum-based compounds in the future.
authors.affiliation: College of Chemistry & Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Hebei University, Baoding, People's Republic of China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Liu
authors.forename: Jinchao
authors.initials: J
authors.lastname: Zhang
authors.forename: Guifang
authors.initials: G
authors.lastname: Wang
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Liu
authors.forename: Shuxiang
authors.initials: S
authors.lastname: Wang
authors.forename: MengSu
authors.initials: M
authors.lastname: Yang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D001862:Bone Resorption / Q000139:chemically induced* / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D059165:Hormesis; D007811:Lanthanum / Q000494:pharmacology* / Q000506:poisoning; D051379:Mice; D009994:Osmolar Concentration; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D015675:Osteocalcin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D053495:Osteopontin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D015415:Biomarkers; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D012333:RNA, Messenger; C493716:Runx2 protein, mouse; C506896:Spp1 protein, mouse; C028521:lanthanum chloride; D015675:Osteocalcin; D053495:Osteopontin; D007811:Lanthanum