Shin DY, et al. Yonsei Med J. 2014 Mar;55(2):476-481. https://doi.org/10.3349/ymj.2014.55.2.476

Bone loss is considered to begin with menopause in women and later in life in men; however, several recent studies have reported that bone loss began in young adults. There are still discordant results concerning age-related changes in bone mineral density (BMD), especially in nonvertebral bone. The objective of the study was to investigate the age-related changes in BMD in Korean youth. This was a population-based, cross-sectional study from the Fourth Korea National Health and Nutrition Examination Surveys. A total 10,575 Korean (4,731 males and 5,844 females) aged 10-80 yr were included. BMD at the spine and hip was measured using dual X-ray absorptiometry. Age-related bone loss at the femoral neck in males occurred continuously with temporary acceleration phase after achieving peak bone mass (PBM). In contrast, age-related bone loss at total hip in both sexes and femoral neck in females showed three obvious phases: acceleration, consolidation, and then the second acceleration phase after reaching PBM. Interestingly, this pattern of bone loss was more significant in the total hip and thus showed the acceleration phase until the late 20s and the consolidation phase until the late 40s. Early accelerated loss of BMD was not observed at the lumbar spine in each sex. Although body mass index and body fat percentage were more related with BMD than other clinical parameters, they could not explain the early accelerated loss of BMD at the femur. There was an accelerated bone loss at the femur in both sexes during early adulthood and more than 60% of the bone loss before age 50 yr occurred during this period.

Recent functional genomic studies revealed that the oncogenic activity of focally amplified lncRNA on chromosome 1 (FAL1, ENSG00000228126) contributes to tumor growth by p21 repression in human cancers. However, the expression of FAL1 was not investigated in papillary thyroid cancer (PTC). We aimed to determine if FAL1 was up-regulated in PTC compared to paired contralateral normal thyroid tissues, and to investigate the potential targets of this lncRNA and its clinicopathological significance in PTC. We analyzed FAL1 and p21 expression levels in 100 PTC samples and matched normal thyroid tissue by qRT-PCR. Using lncRNA microarray data from the Gene Expression Omnibus (accession no. GSE61763), we explored potential targets of FAL1 by Gene Set Enrichment Analysis, followed by verification by qRT-PCR in our PTC samples. A cross-sectional observational study was conducted to investigate the relationship between patients' clinicopathological features and FAL1 expression. FAL1 expression was significantly higher in PTC than in paired normal thyroid tissues (paired t test, P < 0.001). p21 mRNA expression was also increased, not decreased, in PTC, and had no correlation with FAL1 expression (r = 0.0897, P = 0.4002). Gene Set Enrichment Analysis, using publicly available microarray data, indicated that a gene set related to the cell cycle, including E2F transcription factors 1 and 2, and cyclin D1, was coordinately enriched among samples with high FAL1 expression. A volcano plot showed that E2F1, E2F2, and VEGFA mRNAs were increased in the high FAL1 samples. In clinicopathological analyses, multifocality was more frequently observed in PTC patients with high FAL1 (P = 0.018). Multivariate analysis showed that high FAL1 expression increased the risk of multifocality (after adjustment for clinical variables, OR = 4.019, CI = 1.041-11.020, P = 0.043). FAL1 may have a role in cell-cycle progression and may be associated with aggressive tumor behavior in PTC.

Significance: Glucocorticoids are well known to play a major role in obesity, but underlying mechanisms have been obscure. We demonstrate that the small G protein Dexras1, first identified based on its dramatic induction by glucocorticoids, mediates adipogenic differentiation of preadipocytes, as well as diet-induced obesity in intact rodents. Thus, the adipogenesis of preadipocytes is abolished by Dexras1 deletion and selectively induced by Dexras1 expression. Relevance to intact animals is evident from our experiments wherein diet-induced obesity is prevented in mice with knockout of Dexras1. Thus, pharmacotherapy involving Dexras1 may afford a promising approach to the therapy of obesity.