Bone morphogenetic protein 2 (BMP-2) is a critical growth factor that directs osteoblast differentiation and bone formation. Phosphoinositide-phospholipase Cbeta 1 (PLCbeta1) 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 PLCbeta1. Here, the function of PLCbeta1 in the osteogenic differentiation was investigated. Briefly, in C2C12 cells treated with BMP-2 we assist to a remarkable increase in PLCbeta1 protein and mRNA expression. The data regarding the influence on differentiation demonstrated that PLCbeta1 promotes osteogenic differentiation by up-regulating alkaline phosphatase (ALP). Moreover, PLCbeta1 is present in the nuclear compartment of these cells and overexpression of a cytosolic-PLCbeta1mutant (cyt-PLCbeta1), 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 PLCbeta1 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 PLCbeta1 and promotes C2C12 BMP-2-induced osteogenesis by targeting PLCbeta1. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
BMP-2 Induced Expression of PLCbeta1 That Is a Positive Regulator of Osteoblast Differentiation.
Blalock W;Piazzi M;
2016
Abstract
Bone morphogenetic protein 2 (BMP-2) is a critical growth factor that directs osteoblast differentiation and bone formation. Phosphoinositide-phospholipase Cbeta 1 (PLCbeta1) 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 PLCbeta1. Here, the function of PLCbeta1 in the osteogenic differentiation was investigated. Briefly, in C2C12 cells treated with BMP-2 we assist to a remarkable increase in PLCbeta1 protein and mRNA expression. The data regarding the influence on differentiation demonstrated that PLCbeta1 promotes osteogenic differentiation by up-regulating alkaline phosphatase (ALP). Moreover, PLCbeta1 is present in the nuclear compartment of these cells and overexpression of a cytosolic-PLCbeta1mutant (cyt-PLCbeta1), 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 PLCbeta1 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 PLCbeta1 and promotes C2C12 BMP-2-induced osteogenesis by targeting PLCbeta1. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
