Search

Loss of Sostdc1, a growth factor paralogous to Sost, causes the formation of ectopic incisors, fused molars, abnormal hair follicles, and resistance to kidney disease. Sostdc1 is expressed in the periosteum, a source of osteoblasts, fibroblasts and mesenchymal progenitor cells, which are critically important for fracture repair. Here, we investigated the role of Sostdc1 in bone metabolism and fracture repair. Mice lacking Sostdc1 (Sostdc1(-/-)) had a low bone mass phenotype associated with loss of trabecular bone in both lumbar vertebrae and in the appendicular skeleton. In contrast, Sostdc1(-/-) cortical bone measurements revealed larger bones with higher BMD, suggesting that Sostdc1 exerts differential effects on cortical and trabecular bone. Mid-diaphyseal femoral fractures induced in Sostdc1(-/-) mice showed that the periosteal population normally positive for Sostdc1 rapidly expands during periosteal thickening and these cells migrate into the fracture callus at 3days post fracture. Quantitative analysis of mesenchymal stem cell (MSC) and osteoblast populations determined that MSCs express Sostdc1, and that Sostdc1(-/-) 5day calluses harbor >2-fold more MSCs than fractured wildtype controls. Histologically a fraction of Sostdc1-positive cells also expressed nestin and α-smooth muscle actin, suggesting that Sostdc1 marks a population of osteochondral progenitor cells that actively participate in callus formation and bone repair. Elevated numbers of MSCs in D5 calluses resulted in a larger, more vascularized cartilage callus at day 7, and a more rapid turnover of cartilage with significantly more remodeled bone and a thicker cortical shell at 21days post fracture. These data support accelerated or enhanced bone formation/remodeling of the callus in Sostdc1(-/-) mice, suggesting that Sostdc1 may promote and maintain mesenchymal stem cell quiescence in the periosteum.

Type 1 diabetes mellitus (T1DM) patients have osteopenia and impaired fracture healing due to decreased osteoblast activity. Further, no adequate treatments are currently available that can restore impaired healing in T1DM; hence a significant need exists to investigate new therapeutics for treatment of orthopedic complications. Sclerostin (SOST), a WNT antagonist, negatively regulates bone formation, and SostAb is a potent bone anabolic agent. To determine whether SOST antibody (SostAb) treatment improves fracture healing in streptozotocin (STZ) induced T1DM mice, we administered SostAb twice weekly for up to 21days post-fracture, and examined bone quality and callus outcomes at 21days and 42days post-fracture (11 and 14weeks of age, respectively). Here we show that SostAb treatment improves bone parameters; these improvements persist after cessation of antibody treatment. Markers of osteoblast differentiation such as Runx2, collagen I, osteocalcin, and DMP1 were reduced, while an abundant number of SP7/osterix-positive early osteoblasts were observed on the bone surface of STZ calluses. These results suggest that STZ calluses have poor osteogenesis resulting from failure of osteoblasts to fully differentiate and produce mineralized matrix, which produces a less mineralized callus. SostAb treatment enhanced fracture healing in both normal and STZ groups, and in STZ+SostAb mice, also reversed the lower mineralization seen in STZ calluses. Micro-CT analysis of calluses revealed improved bone parameters with SostAb treatment, and the mineralized bone was comparable to Controls. Additionally, we found sclerostin levels to be elevated in STZ mice and β-catenin activity to be reduced. Consistent with its function as a WNT antagonist, SostAb treatment enhanced β-catenin activity, but also increased the levels of SOST in the callus and in circulation. Our results indicate that SostAb treatment rescues the impaired osteogenesis seen in the STZ induced T1DM fracture model by facilitating osteoblast differentiation and mineralization of bone.

Under the background of One Belt and One Road, western cultural factors, especially western taboo culture, should be taken into consideration in the image design of tourism products when developing tourism. Based on the principle of image positioning, this paper puts forward some preliminary suggestions in this regard.

By optical microscopy and SEM-energy spectrometry, some phenomena that relate to lake-bottom hydrothermal activities, such as the presence of siliceous rocks, ankerite laminar deposits, evidence for marcasite brassil anhydrite symbiosis systems and authigenetic albite filling in early diagenetic fractures, have been discovered in the Chang 7 high-quality source beds of the Yanchang Formation, Ordos Basin. Various geochemical data of the Chang 7 high-quality source rocks testify further to the existence of lake-bottom hydrothermal activities, and they include abnormally abundant S2- content (on average 7.37%), Mo, Cu, U and Mn positive anomalies, high ratios of U to Th, the positive carbon isotope composition of crystalline ankerite (δ13C from 2.88 to 3.03‰), depleted oxygen isotope composition (δ18O PDB from −16.41 to −16.17‰), the enrichment of microelements like Cu and Mn, and isotopically enriched in 34S sulfur isotope compositions of strawberry-shaped pyrite (δ34S CDT from 2.37 to 5.90‰). In the early sedimentary period of the Chang 7, the activation of floor ruptures by violent regional structural activities was a dynamic factor that produced lake-bottom hydrothermal activities. The hydrothermal activities played an important role in accelerating the extensive development of the Chang 7 high-quality source rocks. 摘 要: 光学显微镜和扫描电子显微镜-能谱仪观测在鄂尔多斯盆地延长组长7优质烃源层中发现了硅质岩、铁白云石纹层沉积、白铁矿-黄铁矿-硬石膏共生体系、早期成岩缝中的自生钠长石充填作用等可能与湖底热水活动有关的现象。能进一步佐证同期湖底热水活动存在的证据还有：长7优质烃源岩中异常高的二价硫含量（平均7.37%），Mo、Cu、U、Mn等微量元素的显著正异常特征，高的U/Th值，微晶铁白云石纹层偏重的碳同位素组成（2.88‰～3.03‰)、偏轻的氧同位素组成（－16.41‰～－16.17‰）和富集Cu、Mn等微量元素的特征，莓状黄铁矿偏正的硫同位素组成（2.37‰～5.90‰）特征等。长7段沉积期始，强烈的区域构造活动对基底断裂的激活作用是产生湖底热水活动的动力学因素，湖底热水活动对长7优质烃源岩的大规模发育具有重要的促进作用。图6表1参14 Key words: lake-basin expansion, lake-bottom hydrothermal activity, high-quality source rock, Late Triassic, Ordos Basin