Roles of irregularity of pore morphology in osteogenesis of Voronoi scaffolds: From the perspectives of MSC adhesion and mechano-regulated osteoblast differentiation.

Bone scaffolds designed based on the Voronoi-tessellation algorithm have been increasingly studied owing to their structural similarity with natural cancellous bone. The irregularity of pore morphology (IPM) influences the osteogenesis efficiency of Voronoi scaffolds since it may alter the static and hydromechanical microenvironments for the initial adhesion and mechano-regulated osteoblast differentiation (MrOD) of mesenchymal stem cells (MSCs). In this work, animal experiments were conducted to explore the relationship between IPM and osteogenesis efficiency in Voronoi scaffolds. A computational fluid dynamics (CFD) analysis based on discrete phase models was performed to predict the efficiency of MSC adhesion in different IPMs. Another combined finite element and CFD analysis based on the mechano-regulation algorithm was performed to predict the influence of IPM on the MrOD of the adhesive MSCs. The results showed that the osteogenesis efficiency of the Voronoi scaffolds increased as the IPM rose from low to moderate and then dropped as the IPM further rose. Same trends were also found in the MSC adhesion and MrOD, which caused by the changes of strain tensors on the strut surface and the tortuosity and fluid velocity of the fluid pathway. Moderate IPM induced the highest osteogenesis efficiency owing to its highest efficiencies of MSC adhesion and MrOD. This work identified the optimal IPM for the osteogenesis of Voronoi scaffolds and clarified its biomechanical mechanisms from the adhesion and mechano-regulated differentiation of MSCs, which is of great importance for guiding Voronoi scaffold design when it is used for bone defect repair.

Long non-coding RNA NEAT1 mediates MPTP/MPP+-induced apoptosis via regulating the miR-124/KLF4 axis in Parkinson's disease.

Accumulating evidence suggests that dysregulation of long non-coding RNAs is closely associated with various human diseases, including Parkinson's disease (PD). However, the role of nuclear-enriched abundant transcript 1 (NEAT1) in the PD process remains unclear. The number of TH+ cells was reduced, and the expression levels of NEAT1 and Krüppel-like factor 4 (KLF4) were increased in the midbrain of MPTP-HCl-treated mice. In addition, the expression of cleaved-caspase-3 (cleaved-casp-3) and Bax (apoptosis-related proteins) was increased, while the expression of Bcl-2 (anti-apoptotic protein) was reduced in MPTP-HCl-treated mice. The expression levels of NEAT1 and KLF4 were increased in MPP+-treated SH-SY5Y cells. Knockdown of NEAT1 promoted cell viability and decreased apoptosis in MPP+-treated SH-SY5Y cells, which could be reversed by upregulating KLF4. KLF4 was verified as a direct target of miR-124, and miR-124 could particularly bind to NEAT1. Downregulation of NEAT1 significantly increased cell viability and decreased apoptosis by regulating miR-124 expression in MPP+-treated SH-SY5Y cells. Additionally, interference of NEAT1 increased the number of TH+ cells and miR-124 expression, while reduced apoptosis and expression of KLF4 in vivo. NEAT1 knockdown increased cell viability and suppressed apoptosis in PD via regulating the miR-124/KLF4 axis, providing a promising avenue for the treatment of PD.