Objective. To investigate the function of NAT10 in mesenchymal stem cell (MSC) osteogenic differentiation and study the mechanism by which NAT10 affects MSC osteogenesis by mediating Gremlin 1 N4-acetylcytidine (ac4C) modification. Methods. Osteogenic differentiation of MSCs was induced, and the osteogenic ability was evaluated with alizarin red S (ARS) and alkaline phosphatase (ALP) assays. The NAT10 expression level during MSC osteogenesis was measured by western blot (WB). MSCs were transfected with lentiviruses to inhibit (Sh-NAT10) or overexpress NAT10 (Over-NAT10), and the osteogenic differentiation ability was assessed by ARS, ALP, and osteogenic gene marker assays. β-Catenin, Akt, and Smad signaling pathway component activation levels were assessed, and the expression levels of key Smad signaling pathway molecules were determined by PCR and WB. The Gremlin 1 mRNA ac4C levels were analyzed using RIP-PCR, and the Gremlin 1 mRNA degradation rate was determined. Sh-Gremlin 1 was transfected to further investigate the role of NAT10 and Gremlin 1 in MSC osteogenesis. Results. During MSC osteogenesis, NAT10 expression, ARS staining, and the ALP level gradually increased. Decreasing NAT10 expression inhibited, and increasing NAT10 expression promoted MSC osteogenic differentiation. NAT10 affected the BMP/Smad rather than the Akt and β-Catenin signaling pathway activation by regulating Gremlin 1 expression. The Gremlin 1 mRNA ac4C level was positively regulated by NAT10, which accelerated Gremlin 1 degradation. Sh-Gremlin 1 abolished the promotive effect of NAT10 on MSC osteogenic differentiation. Conclusion. NAT10 positively regulated MSC osteogenic differentiation through accelerating the Gremlin 1 mRNA degradation by increasing its ac4C level. These results may provide new mechanistic insight into MSC osteogenesis and bone metabolism in vivo.
Background: Frequent in-out-in femoral neck screws were reported potential huge iatrogenic-injury risks, related to axial safe target area (ASTA) of femoral neck screws channel. However, orientated-quantitative ASTA based on stable coordinate system was unreported before. Methods: Three-dimensional reconstruction was performed on computed tomography (CT) images of 139 intact normal hips, and the intersection area, defined as ASTA, was obtained by superimposing the axial CT images of each femoral neck. Taking anterior cortex of femoral neck basilar (AC-FNB) as landmark, a coordinate system was established to measure the anterior–posterior diameter (D-AP), the superior–inferior diameter (D-SI) and the oblique angle respectively. Each intersection was overlaid up to the axial CT images to determine the coronal location of the ASTA boundaries. Results: Each ASTA presented an inclined rounded triangle with a flat anterior base coincided with AC-FNB. There were significant sex differences in D-SI (male: 33.6±2.3 vs. female: 29.4±1.9 mm) and D-AP (male: 25.3±2.1 vs. 21.9±1.9 mm), P<0.001. D-SI was found to be positively correlated with D-AP (R 2=0.6). All fluoroscopic visible border isthmus completely matched the corresponding ASTA boundaries. The oblique angle was 5–53° (male: 28.1±10.3°, female: 27.1±8.2°) without significant difference between sexes. Conclusion: The intersection method was employed to conveniently acquire orientated-quantitative individualized ASTA. Under this coordinate system, x-ray data of screws could be converted to axial coordinates in CT ASTA, which could help surgeons design combined screws configuration preoperatively and evaluate quantitatively their axial position intraoperatively.
Study Design: A prospective study of in vitro animal. Objection: To compare the biomechanics of cortical bone trajectory screw (CBT) and bone cement screw (BC) in an isolated porcine spinal low bone mass model. Summary of Background Data: The choice of spinal fixation in patients with osteoporosis remains controversial. Is CBT better than BC? Research on this issue is lacking. Methods: Ten porcine spines with 3 segments were treated with EDTA decalcification. After 8 weeks, all the models met the criteria of low bone mass. Ten specimens were randomly divided into groups, group was implanted with CBT screw (CBT group) and the other group was implanted with bone cement screw (BC group). The biomechanical material testing machine was used to compare the porcine spine activities of the two groups in flexion, extension, bending, and axial rotation, and then insertional torque, pull-out force, and anti-compression force of the 2 groups were compared. Independent sample t test was used for comparison between groups. Results: Ten 3 segments of porcine spine models with low bone mass were established, and the bone mineral density of all models was lower than 0.75 g/cm2. There is no difference between the CBT and BC groups in flexion, extension, bending, and axial rotation angle, P>0.05. However, there were significant differences between the 2 groups and the control group, with P<0.01. The 2 groups significantly differed between the insertional torque (P=0.03) and the screw pull-out force (P=0.021). The anti-compression forces between the 2 groups have no significant difference between the two groups (P=0.946). Conclusions: The insertional torque and pull-out force of the CBT were higher than those of the BC in the isolated low bone porcine spine model. The range of motion and anti-compression ability of the model was similar between the 2 fixation methods.
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