Foxf2 represses bone formation via Wnt2b/ß-catenin signaling.

Differentiation of mesenchymal stem cells (MSCs) into osteoblasts is a critical process for proper skeletal development and acquisition/maintenance of bone mass. However, since this regulatory mechanism has not yet been fully elucidated, the treatment of severe osteoporosis and fractures is a challenge. Here, through a comprehensive analysis of gene expression during the differentiation of MSCs into osteoblasts, we show that the forkhead transcription factor Foxf2 is a crucial regulator of this process. Foxf2 expression transiently increased during MSC osteoblastic differentiation. Overexpression of Foxf2 in MSCs inhibited osteoblastic differentiation, and conversely, knockdown of Foxf2 expression promoted this process. Osteoprogenitor-specific Foxf2 knockout mice developed a high bone mass phenotype due to increased bone formation. RNA-seq analysis and molecular experiments revealed that Foxf2 regulation of bone formation is mediated by Wnt2b. Knockdown of Foxf2 in mouse femurs enhanced bone regeneration in vivo. FOXF2 expression was correlated with hip bone mineral density in postmenopausal women with low bone mass. Finally, inhibition of FOXF2 promoted osteoblastic differentiation of human MSCs. This study uncovers a critical role of Foxf2 in the differentiation of MSCs into osteoblasts and provides insight into the pathogenesis associated with bone-related diseases such as osteoporosis and nonunion after fracture.

Detection of CDH1 gene methylation of suspension cells in abdominal lavage fluid from colorectal cancer patients and its clinical significance / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To detect the CDH1 gene methylation of suspension cells in intraoperative abdominal lavage fluid from colorectal cancer patients, and to examine its association with clinicopathology and prognosis.</p><p><b>METHODS</b>Real-time methylation-specific polymerase chain reaction (qMSP) was used to investigate the methylation status of the CDH1 gene promoter 5'-CpG islands from intraoperative abdominal lavage fluid in 102 patients with colorectal cancer. The associations between methylation of CDH1 genes and clinicopathologic features and prognosis were investigated.</p><p><b>RESULTS</b>Among the 102 colorectal cancer patients, aberrant methylation of CDH1 gene was detected in 47 patients. Significant associations were found between CDH1 methylation status and tumor size, growth pattern, differentiation, distant metastasis, and clinical staging (all P<0.05). The median progression-free survival was 25.98 months for CDH1 methylation group and 41.36 months for non-methylated group, and the difference was statistically significant (P<0.01). Cox model analysis revealed that CDH1 methylation status in intraoperative peritoneal lavage fluid was an independent factor associated with postoperative survival in colorectal cancer patients (50.23% vs. 86.51%, P=0.001).</p><p><b>CONCLUSIONS</b>Colorectal cancer patients with aberrant methylation of 5'-CpG of CDH1 gene promoter of suspension cells in abdominal lavage have higher malignancy, more metastasis and worse prognosis.</p>