Messenger RNAs (mRNAs) function as mobile signals for cell-to-cell communication in multicellular organisms. The KNOTTED1 (KN1) homeodomain family transcription factors act non–cell autonomously to control stem cell maintenance in plants through cell-to-cell movement of their proteins and mRNAs through plasmodesmata; however, the mechanism of mRNA movement is largely unknown. We show that cell-to-cell movement of a KN1 mRNA requires ribosomal RNA–processing protein 44A (AtRRP44A), a subunit of the RNA exosome that processes or degrades diverse RNAs in eukaryotes. AtRRP44A can interact with plasmodesmata and mediates the cell-to-cell trafficking of KN1 mRNA, and genetic analysis indicates that AtRRP44A is required for the developmental functions of SHOOT MERISTEMLESS, an Arabidopsis KN1 homolog. Our findings suggest that AtRRP44A promotes mRNA trafficking through plasmodesmata to control stem cell–dependent processes in plants.
Vertebral fractures in beta-thalassemia major are increasingly found because of the longer life expectancy of patients, with a major negative impact on their quality of life. We performed a retrospective cross-sectional study to investigate the prevalence of vertebral deformities in thalassemic patients and to identify their best dual-energy X-ray absorptiometry (DXA) predictor among trabecular bone score (TBS), bone mineral density (BMD), and Z-score. Eighty-two outpatients with beta-thalassemia major on regular conventional treatment were studied at a single academic center. All patients underwent plain thoracic-lumbar spine X-rays and lumbar DXA to assess the number and the severity of vertebral deformities (Genant's method), the spinal deformity index, lumbar spine DXA parameters (BMD, TBS, and Z-score), and the presence of platyspondyly. Twenty-nine patients (35%) had vertebral deformities and showed significantly lower TBSs than the remainders (1.141 ± 0.083 vs 1.254 ± 0.072, p < 0.0001). The analysis of variance of the TBS between the group of patients without vertebral deformities (spinal deformity index = 0) and the remaining groups showed a significant difference (p < 0.001). The TBS had better sensitivity (86.2%), specificity (75.5%), and diagnostic accuracy (79.3%) than BMD and Z-score in discriminating patients with and without vertebral deformities. Combining the TBS with the BMD or the Z-score showed that the diagnostic accuracy of the first in discriminating patients with and without vertebral deformities improved from 79.3% to 85.4% and 87.8%, respectively. The presence of platyspondyly was a significant predictor of vertebral deformities in the multivariate model. Vertebral deformities in well-treated patients with beta-thalassemia major are common and are often unrecognized. In our hands, the TBS was better than the BMD and the Z-score in predicting vertebral deformities. Plain X-rays of the spine should be performed also in asymptomatic patients, especially when the TBS is low.
Trabecular bone score (TBS) may detect subjects with a more degraded microarchitecture but whose bone mineral density (BMD) reflects normal or osteopenia. The purpose of this study was to evaluate whether age and body sizes were associated with the discordance between BMD and TBS. We analyzed BMD and TBS in 1505 Korean women over 40 yr of age who had no history of osteoporotic fractures or conditions that affect bone metabolism. We considered 3 groups to have TBS values that reflected a more degraded TBS than their BMD values: (1) normal BMD but partially degraded TBS, (2) normal BMD but degraded TBS, and (3) osteopenia but degraded TBS. We compared subjects in these 3 groups with other subjects in terms of age and body sizes, and used multivariable logistic regression to analyze the odds ratios (ORs) for the occurrence of a more degraded TBS than their BMD level using age and body mass index (BMI). One hundred sixty subjects (10.6%) were found to have a more degraded TBS than their BMD level; these subjects were older, heavier, and had higher BMIs than the other subjects. Age (OR: 1.038, 95% confidence interval: 1.020–1.057, p < 0.001) and BMI (OR: 1.223, 95% confidence interval: 1.166–1.283, p < 0.001) were statistically significant in the multivariable analysis for the occurrence of this feature. Women with a more degraded TBS than their BMD level are older and have higher BMIs than the other subjects. It may be helpful to consider the possibility of trabecular bone degradation when clinically evaluating fracture risk in patients who are older or who have high BMIs with normal BMD or osteopenia.
According to reports from small-sized case series, adults with Down syndrome (DS) appear to have lower bone mineral density (BMD) than the general population. The objective of our study was to further characterize the bone mass acquisition curve in an adult DS population. This is a retrospective study of 297 adults with DS from the Adult Down Syndrome Outpatient Clinic of a tertiary care hospital in Madrid, Spain, who underwent a bone densitometry (Hologic QDR-4500W), for clinical purposes between January 2010 and June 2015. The mean age of our sample population was 34 yr (±10.9); 51% were women. Bone mass peak was reached earlier and was lower than the general population (around 20–25 yr), with almost parallel curves. The mean BMD was 0.715 ± 0.12 g/cm2 in femoral neck (FN) and 0.872 ± 0.11 g/cm2 in lumbar spine (LS). According to FN scores, 52% of the subjects were classified as osteopenic and 18% as osteoporotic. According to LS scores, frequencies were 54% and 25%, respectively. BMD was considered inadequate for the age (Z-score < −2 standard deviation) in 18% of the subjects at FN and 40% at LS. BMD at LS was significantly lower in males than in females (52% vs 38%, p < 0.001). Male DS subjects had a 2.58-fold (95% confidence interval: 1.57–4.25) higher risk of developing reduced BMD at LS than females. Persons with DS reach the bone mass peak earlier and this bone mass is lower than the general population. Among subjects with DS, male gender is a risk factor for developing low BMD, especially at LS.
With the objective of being able to assess response to disease or clinical treatment, the densitometry community has long sought the ability to assess short-term change in bone density. The mandible, known to have a high bone turnover, an increased vascularity, and a greater susceptibility to osteoclastic and osteoblastic activities, has long been suggested but has fallen short as a site from which to monitor an early change in the response to a treatment or a disease. The current study developed a method to assess bone density in the superimposed left and right mandibles. Examining a skull in a positioning platform showed that studies between -5.0° and +12.5° from the preferred 0° orientation generated studies that were statistically similar to studies in the preferred orientation. After establishing the distribution of bone density in the mandibles, a software was developed that would execute a search for an area of intermediate content within the body and ramus regions of the mandible; in subsequent studies of the same individual, the analysis software would place the body and ramus regions in the same location without operator dependence. Studies in a population of subjects showed that the density in the body and ramus regions varied independently and that the density in these regions was independent of age. Repeat studies with repositioning showed repeatability of 1.73% and 2.44% for the body and ramus, resulting in computed least significant change limits of 4.84% for the body and 6.83% for the ramus. Examining 45 subjects undergoing treatment for osteoporosis up to over 46 wk showed 22 (49%) subjects with an increase in 1 of the mandible sites, suggesting a benefit from treatment, whereas 12 (27%) subjects showed a decrease in both mandible sites, suggesting a poor response to treatment. We conclude that applying the methodology and allowing the software to locate and define regions of interest allow assessments of change in the bone mineral content at the mandible that will reflect early changes occurring with disease or treatment.