title: BMP-2 Induced Expression of PLCβ1 That is a Positive Regulator of Osteoblast Differentiation.
abstract: Bone morphogenetic protein 2 (BMP-2) is a critical growth factor that directs osteoblast differentiation and bone formation. Phosphoinositide-phospholipase Cβ 1 (PLCβ1) plays a crucial role in the initiation of the genetic program responsible for muscle differentiation. Differentiation of C2C12 mouse myoblasts in response to insulin stimulation is characterized by a marked increase in nuclear PLCβ1. Here, the function of PLCβ1 in the osteogenic differentiation was investigated. Briefly, in C2C12 cells treated with BMP-2 we assist to a remarkable increase in PLCβ1 protein and mRNA expression. The data regarding the influence on differentiation demonstrated that PLCβ1 promotes osteogenic differentiation by up-regulating alkaline phosphatase (ALP). Moreover, PLCβ1 is present in the nuclear compartment of these cells and overexpression of a cytosolic-PLCβ1mutant (cyt-PLCβ1), which lacks a nuclear localization sequence, prevented the differentiation of C2C12 cells into osteocytes. Recent evidence indicates that miRNAs act as important post transcriptional regulators in a large number of processes, including osteoblast differentiation. Since miR-214 is a regulator of Osterix (Osx) which is an osteoblast-specific transcription factor that is needful for osteoblast differentiation and bone formation, we further investigated whether PLCβ1 could be a potential target of miR-214 in the control of osteogenic differentiation by gain- and loss- of function experiment. The results indicated that inhibition of miR-214 in C2C12 cells significantly enhances the protein level of PLCβ1 and promotes C2C12 BMP-2-induced osteogenesis by targeting PLCβ1.
authors.affiliation: Cell Signaling Laboratory, Department of Biomedical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ramazzotti
authors.affiliation: SC Laboratory of Musculoskeletal Cell Biology, Rizzoli Orthopedic Institute, Bologna, Italy.|Laboratory RAMSES, Rizzoli Orthopedic Institute, Bologna, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bavelloni
authors.affiliation: CNR-National Research Council of Italy, Institute of Molecular Genetics, Bologna, Italy.
authors.forename: William
authors.initials: W
authors.lastname: Blalock
authors.affiliation: Cell Signaling Laboratory, Department of Biomedical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Piazzi
authors.affiliation: Cell Signaling Laboratory, Department of Biomedical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Cocco
authors.affiliation: Cell Signaling Laboratory, Department of Biomedical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Faenza
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D032446:Myoblasts / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D054799:Phospholipase C beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: D055396:Bone Morphogenetic Protein 2; D035683:MicroRNAs; C534781:Mirn214 microRNA, mouse; D054799:Phospholipase C beta; C518034:Plcb1 protein, mouse