Self-Assembled Tetrahedral DNA Nanostructures Promote Adipose-Derived Stem Cell Migration via lncRNA XLOC 010623 and RHOA/ROCK2 Signal Pathway

Abstract

Self-assembled tetrahedral DNA nanostructures (TDNs) with precise sizes have been extensively applied in various fields owing to their exceptional mechanical rigidity, structural stability, and modification versatility. In addition, TDNs can be internalized by mammalian cells and remain mainly intact within the cytoplasm by escaping degradation by nucleases. Here, we studied the effects of TDNs on cell migration and the underlying molecular mechanisms. TDNs remarkably enhanced the migration of rat adipose-derived stem cells and down-regulated the long noncoding RNA (lncRNA) XLOC 010623 to activate the mRNA expression of Tiam1 and Rac1. Furthermore, TDNs highly up-regulated the mRNA and protein expression of RHOA, ROCK2, and VCL. These results indicate that TDNs suppressed the transcription of lncRNA XLOC 010623 and activated the TIAM1/RAC1 and RHOA/ROCK2 signaling pathways to promote cell migration. On the basis of these findings, TDNs show a high potential for application in tissue repair and regenerative medicine as a functional three-dimensional DNA nanomaterial.

Effect of tetrahedral DNA nanostructures on proliferation and osteogenic differentiation of human periodontal ligament stem cells

“…In Figure 1A, A synthesis diagram shows the tetrahedral structure of TDNs formed by self-folding of four pre-synthesized ssDNA based on complementary base pairing. 25 An 8% PAGE was performed in order to demonstrate that the tetrahedral DNA nanostructure was successfully synthesized ( Figure 1B). Furthermore, we used AFM to explore the shape of TDNs, which displayed that it had a triangular particle, diverse in size, about 2-3 nm in width and about 17 nm in height ( Figure 1C).…”

“…[17][18][19] There are various DNA nanomaterial structures, such as one-dimensional DNA structures including linear DNA, two-dimensional DNA structures, which self-assemble to form planar structures such as a triangle, a pentagram and three-dimensional DNA structures, including octahedron and dodecahedron. 25 Considering all of this evidence, a hypothesis was proposed that TDNs may facilitate proliferation and promote osteogenic differentiation of PDLSCs by regulating the Wnt/β-catenin signalling pathway. Therefore, TDN has great potential for application in molecular diagnosis, drug delivery and bioimaging.…”

“…In addition, because of the merits of excellent biocompatibility, high stability, low toxicity, fast degradation and direct cellular uptake through endocytosis without carriers, TDNs have been applied to tissue engineering in order to modulate the biological behaviours of stem cells, including proliferation, migration and differentiation. 25 Therefore, PDLSCs were exposed to TDNs, with the purpose of systematically exploring the role of TDNs in the proliferation and osteogenic differentiation of PDLSCs. The results indicated that TDNs had a tremendous potential for application in PDLSC-based bone regeneration.…”

Substrate stiffness regulated migration and angiogenesis potential of A549 cells and HUVECs

“…The co-culture system was also used for investigating the effects of the A549 cells have on the migration of HUVECs, as described previously (Shi, Peng, et al, 2016). The cell culture was the same as described above (The transwell inserts were 8 µm pore diameter).…”

Stiffness regulates the proliferation and osteogenic/odontogenic differentiation of human dental pulp stem cells via the WNT signalling pathway

“…In recent years, tissue engineering has been widely focused and considered an important approach to restore damaged tissues and organs. [1][2][3][4] The emergence of tissue engineering technology enables the successful isolation of dental pulp stem cells (DPSCs) and the use of DPSCs for repair of bone tissues or dentin-pulp tissue and even for the construction of natural teeth. [5][6][7][8] DPSCs are tissuespecific stem cells with a high proliferation rate, self-renewal capability and high accessibility.…”