20 research outputs found
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Loss of p53 in mesenchymal stem cells promotes alteration of bone remodeling through negative regulation of osteoprotegerin.
p53 plays a pivotal role in controlling the differentiation of mesenchymal stem cells (MSCs) by regulating genes involved in cell cycle and early steps of differentiation process. In the context of osteogenic differentiation of MSCs and bone homeostasis, the osteoprotegerin/receptor activator of NF-κB ligand/receptor activator of NF-κB (OPG/RANKL/RANK) axis is a critical signaling pathway. The absence or loss of function of p53 has been implicated in aberrant osteogenic differentiation of MSCs that results in higher bone formation versus erosion, leading to an unbalanced bone remodeling. Here, we show by microCT that mice with p53 deletion systemically or specifically in mesenchymal cells possess significantly higher bone density than their respective littermate controls. There is a negative correlation between p53 and OPG both in vivo by analysis of serum from p53+/+, p53+/-, and p53-/- mice and in vitro by p53 knockdown and ChIP assay in MSCs. Notably, high expression of Opg or its combination with low level of p53 are prominent features in clinical cancer lesion of osteosarcoma and prostate cancer respectively, which correlate with poor survival. Intra-bone marrow injection of prostate cancer cells, together with androgen can suppress p53 expression and enhance local Opg expression, leading to an enhancement of bone density. Our results support the notion that MSCs, as osteoblast progenitor cells and one major component of bone microenvironment, represent a cellular source of OPG, whose amount is regulated by the p53 status. It also highlights a key role for the p53-OPG axis in regulating the cancer associated bone remodeling
Distribution and characteristics of loess landslides triggered by the 1920 Haiyuan Earthquake, Northwest of China
On December 16, 1920, an earthquake with a magnitude of 8.5 occurred in Haiyuan County, Ningxia Hui Autonomous Region, Northwest of China. This earthquake triggered several thousand loess landslides which resulted in thousands of deaths and blockages of rivers. The distribution and characteristics of the landslides triggered by the Haiyuan Earthquake in loess areas were studied using satellite images and field investigation. A total of about 3700 landslides with a cumulative area of about 177 km2 were interpreted over an area of 21,000 km2. It was found that landslides triggered by the earthquake were concentrated in a western of 40–55 km from the Haiyuan fault. Landslides were concentrated near ridge crests, with 65.7% of the landslides originating in the upper quadrant of slopes. The aspects of the landslides triggered by the Haiyuan Earthquake were parallel to the faults and there is no back-direction effect in landslides triggered by Haiyuan earthquake. These landslides have long run-out distances(travel distance (L)/height different (H) > 0.6) and deposited materials in river channels, forming 51 dammed lakes that still exist. The relationship between the area (A) and volume (V) of the landslides is V = 4.170 × A1.086. Based on the relationship between number and volume of landslide and the magnitude of earthquake, >100,000 landslides with a cumulative volume of 0.5 × 1010 m3 were triggered by the Haiyuan Earthquake. As loess is sensitive to liquefaction during an earthquake and tends to produce landslides with long travel distances. Hence, the loess depth, slope and geological stresses are the primary factors responsible for the high density of landslides in this region