An Oligodeoxynucleotide That Induces Differentiation of Bone Marrow Mesenchymal Stem Cells to Osteoblasts in Vitro and Reduces Alveolar Bone Loss in Rats with Periodontitis

Abstract

To investigate the effect of oligodeoxynucleotides (ODNs) on the differentiation of rat bone marrow mesenchymal stem cells (BMSCs) to osteoblasts, in order to find a candidate ODN with potential for the treatment of periodontitis, a series of ODNs were designed and selected to test their effect on the promotion of the differentiation of BMSCs to osteoblasts in vitro and on the repair of periodontal tissue in rats with periodontitis. It was found that MT01, one of the ODNs with the sequences of human mitochondrial DNA, stimulated the proliferation of BMSCs, the differentiation of BMSCs to osteoblasts and mRNA expression of bone-associated factors including Runx2, Osterix, OPG, RANKL and collagen I in vitro. In vivo study showed that MT01 prevented the loss of alveolar bone in the rats with periodontitis and induced the production of proteins of OPG and Osterix in the bone tissue. These results indicated that MT01 could induce differentiation of BMSCs to osteoblasts and inhibit the alveolar bone absorption in rats with periodontitis.

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

“…Our previous studies have found that ODN MT01 could regulate the balance of bone formation and resorption, and that it therefore has a great potential in the rebuilding of alveolar bone. [5][6][7] Here we applied PEN as a carrier for MT01 delivery with the aim to enhance its cellular uptake capability and its stability. Different types of PEI are regarded as the most effective nonviral gene vectors due to their ability to reduce the negative charge of DNA and to partially condense its normally large hydrodynamic volume and the ability to escape from lysosomes.…”

“…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.…”

Porphyromonas gingivalis lipopolysaccharides regulate functions of bone marrow mesenchymal stem cells

“…By their multipotency, BMMSCs hold great promise for clinical applications of achieving tissue regeneration. Recent studies have shown that they contribute to formation of all periodontal tissues, including periodontal ligament, cementum, and alveolar bone, thus might be an alternative cell source to achieve periodontal regeneration . However, precise mechanisms underlying these effects had remained poorly understood, which limited advanced application of BMMSCs for treating periodontitis.…”

The Toll-like receptor ligand, CpG oligodeoxynucleotides, regulate proliferation and osteogenic differentiation of osteoblast

“…Actived TLR9 on osteoblast's surface initiates extracellular signal-regulated protein kinase and P38 to release tumor necrosis factor α, then enhancing the expression of macrophage colony-stimulating factor to regulate osteoclasts [11]. The CpG ODN yet plays a positive role in osteogenic differentiaion of bone mesenchymal stem cells [12] and pre-osteoblasts [13].…”