In this study we investigated if Wnt/β-catenin signaling in mesenchymal progenitor cells plays a role in bone fracture repair and if DKK1-Ab promotes fracture healing through activation of β-catenin signaling. Unilateral open transverse tibial fractures were created in CD1 mice and in β-cateninPrx1ER conditional knockout (KO) and Cre-negative control mice (C57BL/6 background). Bone fracture callus tissues were collected and analyzed by radiography, micro-CT (μCT), histology, biomechanical testing and gene expression analysis. The results demonstrated that treatment with DKK1-Ab promoted bone callus formation and increased mechanical strength during the fracture healing processinCD1 mice. DKK1-Ab enhanced fracture repair by activation of endochondral ossification. The normal rate of bone repair was delayed when the β-catenin gene was conditionally deleted in mesenchymal progenitor cells during the early stages of fracture healing. DKK1-Ab appeared to act through β-catenin signaling to enhance bone repair since the beneficial effect of DKK1-Ab was abrogated in β-cateninPrx1ER conditional KO mice. Further understanding of the signaling mechanism of DKK1-Ab in bone formation and bone regeneration may facilitate the clinical translation of this anabolic agent into therapeutic intervention.

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Abstract:To enhance the quantitative simulation and integrated assessment of non-point source (NPS) pollution in plateau lakes in data-poor regions, a simple and practical NPS assessment method is developed by combining the improved export coefficient model (ECM) and the revised universal soil loss equation (RUSLE). This method is evaluated via application to the Chenghai Lake watershed (Yunnan Province, China), which contains a typical plateau lake. The estimated results reflect the actual situation within the watershed. The total nitrogen (TN) and total phosphorus (TP) loads in the study area in 2014 were 360.35 t/a (44.30% dissolved nitrogen (DN) and 55.70% adsorbed nitrogen (AN)) and 86.15 t/a (71.40% adsorbed phosphorus (AP)), respectively. The southern and eastern portions of the watershed are key regions for controlling dissolved and adsorbed pollutants, respectively. Soil erosion and livestock are the main TN and TP pollution sources in the study area and should be controlled first. Additionally, reasonable and practical suggestions are proposed to minimize water pollution according to a scenario analysis. The method in this study provides a foundation for scientific theories that can be used in water resources protection planning and the method can be applied to the NPS assessment of similar regions with scarce data.