ROCK-TAZ signaling axis regulates mechanical tension-induced osteogenic differentiation of rat cranial sagittal suture mesenchymal stem cells.

Mechanical force across sutures is able to promote suture osteogenesis. Orthodontic clinics often use this biological characteristic of sutures to treat congenital cranio-maxillofacial malformations. However, the underlying mechanisms still remain poorly understood. Craniofacial sutures provide a special growth source and support primary sites of osteogenesis. Here, we isolated rat sagittal suture cells (rSAGs), which had mesenchymal stem cell characteristics and differentiating abilities. Cells were then subjected to mechanical tension (5% elongation, 0.5 Hz; sinusoidal waveforms) showing that mechanical tension could enhance osteogenic differentiation but hardly affect proliferation of rSAGs. Besides, mechanical tension could increase Rho-associated kinase (ROCK) expression and enhance transcriptional coactivator with PDZ-binding motif (TAZ) nuclear translocation. Inhibiting ROCK expression could suppress tension-induced osteogenesis and block tension-induced upregulation of nuclear TAZ. In addition, our results indicated that TAZ had direct combination sites with runt-related transcription factor 2 (Runx2) in rSAGs, and knock-downed TAZ simultaneously decreased the expression of Runx2 no matter with or without mechanical tension. In summary, our findings demonstrated that the multipotency of rSAGs in vitro could give rise to early osteogenic differentiation under mechanical tension, which was mediated by ROCK-TAZ signal axis.

Templated polymers enable selective capture and release of lysophosphatidic acid in human plasma via optimization of non-covalent binding to functional monomers.

The first solid phase extraction materials for selective lysophosphatidic acid (LPA) enrichment from human plasma are described. Molecularly imprinted polymers were designed, synthesized and evaluated as cartridge fillings. They enabled a relatively rapid and simple extraction protocol for LPA without any need for multiple liquid-liquid extraction steps. The five major subspecies of lysophosphatidic acid are readily separated from all other native plasma phospholipids, including those well-known to interfere with LPA quantitation, such as phosphatidylcholine and lysophosphatidylcholine. Outstanding LPA purity is obtained via these solid phase materials in a tandem extraction setup.

In vivo editing of lung stem cells for durable gene correction in mice.

In vivo genome correction holds promise for generating durable disease cures; yet, effective stem cell editing remains challenging. In this work, we demonstrate that optimized lung-targeting lipid nanoparticles (LNPs) enable high levels of genome editing in stem cells, yielding durable responses. Intravenously administered gene-editing LNPs in activatable tdTomato mice achieved >70% lung stem cell editing, sustaining tdTomato expression in >80% of lung epithelial cells for 660 days. Addressing cystic fibrosis (CF), NG-ABE8e messenger RNA (mRNA)-sgR553X LNPs mediated >95% cystic fibrosis transmembrane conductance regulator (CFTR) DNA correction, restored CFTR function in primary patient-derived bronchial epithelial cells equivalent to Trikafta for F508del, corrected intestinal organoids and corrected R553X nonsense mutations in 50% of lung stem cells in CF mice. These findings introduce LNP-enabled tissue stem cell editing for disease-modifying genome correction.

Relationship of the airway size to the mandible distance in Chinese skeletal Class I and Class II adults with normal vertical facial pattern.

OBJECTIVE: This study aims to evaluate the pharyngeal airway dimensions among Chinese adults in relation to Class I and Class II facial skeletal patterns using three-dimensional cone-beam computed tomography (CBCT) images. MATERIALS AND METHODS: A total of 156 initial CBCT images were evaluated, which were classified into skeletal Class I and Class II according to ANB angle with mean (SD) age being 22.56 ± 4.0 years and 22.32 ± 3.6 years. The pharyngeal airway volume, airway area, minimum cross-sectional area (MCA) and the distance from uvula (tip of the soft palate) to mental spine (U-MS distance) were assessed with Dolphin imaging software. RESULTS: Compared with Class I group, Class II group displayed significantly smaller pharyngeal airway volume, airway area and MCA (P <.01, P =0.03, and P =0.008, respectively), and shorter U-MS distance (P <.001). Comparing gender subgroups, the female subgroup showed the smallest airway measurement. Spearman correlation test results showed that the airway volume and area had a significant positive correlation with U-MS distance (r = 0.22, P = 0.005, and r = 0.28, P < 0.005, respectively) and negative correlation with ANB angle (r = -0.23, P = 0.002, and r = -0.21, P = 0.007, respectively). CONCLUSIONS: Pharyngeal airway volume, airway area, MCA, and the U-MS distance were smaller in skeletal Class II than Class I Chinese adult subjects and lower in female Class II subgroup. Additionally, there was a correlation observed between the mandibular distance (U-MS), ANB angle and airway size.