A Specific Oligodeoxynucleotide Promotes the Differentiation of Osteoblasts via ERK and p38 MAPK Pathways

Abstract

A specific oligodeoxynucleotide (ODN), ODN MT01, was found to have positive effects on the proliferation and activation of the osteoblast-like cell line MG 63. In this study, the detailed signaling pathways in which ODN MT01 promoted the differentiation of osteoblasts were systematically examined. ODN MT01 enhanced the expression of osteogenic marker genes, such as osteocalcin and type I collagen. Furthermore, ODN MT01 activated Runx2 phosphorylation via ERK1/2 mitogen-activated protein kinase (MAPK) and p38 MAPK. Consistently, ODN MT01 induced up-regulation of osteocalcin, alkaline phosphatase (ALP) and type I collagen, which was inhibited by pre-treatment with the ERK1/2 inhibitor U0126 and the p38 inhibitor SB203580. These results suggest that the ERK1/2 and p38 MAPK pathways, as well as Runx2 activation, are involved in ODN MT01-induced up-regulation of osteocalcin, type I collagen and the activity of ALP in MG 63 cells.

Enhancing the osteogenic capacity of MG63 cells through N-isopropylacrylamide-modified polyethylenimine-mediated oligodeoxynucleotide MT01 delivery

“…3 In our previous studies, an oligodeoxynucleotide (ODN) that was designed based on human mitochondrial DNA (MT01), was demonstrated to promote the proliferation and activation of osteoblasts and stimulate the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts. [4][5][6][7] However, crucial problems such as poor oligonucleotide stability in the presence of nuclease activity in vitro and in vivo, and low intracellular penetration, would limit its wide application to enhance osteogenic capacity. 8 To overcome these problems, chemical modications of ODNs have been employed, mainly focusing on the phosphodiester backbone and/or the sugar moiety.…”

Epigenetic silencing of HDAC1 by miR-449a upregulates Runx2 and promotes osteoblast differentiation

“…Mesenchymal stem cells can differentiate into mature and functional osteoblasts that produce extracellular matrix proteins and proteins that regulate matrix mineralization (10). Runx2, also known as Cbfa1/AmI3, is a runt domain family protein, which acts as an osteoblast-specific transactivator essential for osteoblast differentiation and bone formation (10)(11)(12)(13)(14).…”

“…Mesenchymal stem cells can differentiate into mature and functional osteoblasts that produce extracellular matrix proteins and proteins that regulate matrix mineralization (10). Runx2, also known as Cbfa1/AmI3, is a runt domain family protein, which acts as an osteoblast-specific transactivator essential for osteoblast differentiation and bone formation (10)(11)(12)(13)(14). Zhang et al (11) showed that commitment of undifferentiated mesenchymal stem cells to an osteoprogenitor lineage was associated with the expression of Runx2, and Runx2 protein levels were significantly upregulated in quiescence (G 0 ) or during proliferative arrest induced by serum deprivation or by contact inhibition of osteoblast cells (15).…”

“…Zhang et al (11) showed that commitment of undifferentiated mesenchymal stem cells to an osteoprogenitor lineage was associated with the expression of Runx2, and Runx2 protein levels were significantly upregulated in quiescence (G 0 ) or during proliferative arrest induced by serum deprivation or by contact inhibition of osteoblast cells (15). Notably, Runx2 -/mice show a complete lack of intramembranous and endochondral ossification, due to the maturation arrest of osteoblasts (10). Runx2 regulates the expression of osteoblast-specific genes, including ALP, type I collagen and osteocalcin (10), and is necessary throughout life to promote the differentiation of new osteoblasts during bone remodeling (10).…”

“…Notably, Runx2 -/mice show a complete lack of intramembranous and endochondral ossification, due to the maturation arrest of osteoblasts (10). Runx2 regulates the expression of osteoblast-specific genes, including ALP, type I collagen and osteocalcin (10), and is necessary throughout life to promote the differentiation of new osteoblasts during bone remodeling (10). The study by Hu et al (16) reported that histone deacetylation suppresses Runx2 transcription.…”