RUNX2 is a master osteogenic transcription factor, and mutations in RUNX2 cause the inherited skeletal disorder cleidocranial dysplasia (CCD). Studies have revealed that RUNX2 is not only a downstream target of the bone morphogenetic protein (BMP) pathway but can also regulate the expression of BMPs. However, the underlying mechanism of the regulation of BMPs by RUNX2 remains unknown. In this project, we diagnosed a CCD patient with a 7.86-Mb heterozygous deletion on chromosome 6 containing all exons of RUNX2 by multiplex ligation-dependent probe amplification (MLPA) and whole-genome sequencing (WGS). Bone marrow mesenchymal stem cells (BMSCs) were further extracted from patient alveolar bone fragments (CCD-BMSCs), an excellent natural model to explore the possible mechanism. The osteogenic differentiation ability of CCD-BMSCs was severely affected by RUNX2 heterozygous deletion. Also, BMP4 decreased most in BMP ligands, and CHRDL1, a BMP antagonist, was abnormally elevated in CCD-BMSCs. Furthermore, BMP4 treatment essentially rescued the osteogenic capacity of CCD-BMSCs, and RUNX2 overexpression reversed the abnormal expression of BMP4 and CHRDL1. Notably, we constructed CRISPR/Cas9 Runx2+/m MC3T3-E1 cells, which simulated a variant in CCD-BMSCs, to exclude the interference of other gene deletions and the heterogeneity of the genetic background of primary cells, and verified all findings from the CCD-BMSCs. Moreover, the luciferase reporter experiment showed that RUNX2 could inhibit the transcription of CHRDL1. Through immunofluorescence, the inhibitory effect of CHRDL1 on BMP4/Smad signaling was confirmed in MC3T3-E1 cells. These results revealed that RUNX2 regulated the BMP4 pathway by inhibiting CHRDL1 transcription. We collectively identified a novel RUNX2/CHRDL1/BMP4 axis to regulate osteogenic differentiation and noted that BMP4 might be a valuable therapeutic option for treating bone diseases.
In order to study the influence of the transparency and crown density of road green belts on particle dispersion, the green belts along Tinjing highway in Tianjin, China, were selected to study in this study and the green space was divided into four types, which respectively were the high crown density-high transparency green space, the low crown density-low transparency green space, the high crown density-low transparency green space and the low crown density-high transparency green space. The particle pollution concentration in sidewalk and green space was researched in the four types of green space. It was concluded that: in the sidewalk, the high crown density-high transparency green space was the most adverse to the diffusion of automobile exhaust pollutants because those contents of pm2.5, pm10 and dust were all the highest; in the green space, the high crown density-high transparency green space and the low crown density-low transparency green space were the most adverse to the diffusion of automobile exhaust pollutants because those contents of pm2.5, pm10 and dust were all the highest. So among the four types of green space, the high crown density-high transparency green space was the most adverse to pollutant diffusion.
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