Aberrant activation of Wnt signaling pathway altered osteocyte mineralization.

Mineralization of bone is a dynamic process, involving a complex interplay between cells, secreted macromolecules, signaling pathways, and enzymatic reactions; the dysregulation of bone mineralization may lead to serious skeletal disorders, including hypophosphatemic rickets, osteoporosis, and rheumatoid arthritis. Very few studies have reported the role of osteocytes - the most abundant bone cells in the skeletal system and the major orchestrators of bone remodeling in bone mineralization, which is owed to their nature of being deeply embedded in the mineralized bone matrix. The Wnt/ß-catenin signaling pathway is actively involved in various life processes including osteogenesis; however, the role of Wnt/ß-catenin signaling in the terminal mineralization of bone, especially in the regulation of osteocytes, is largely unknown. This research demonstrates that during the terminal mineralization process, the Wnt/ß-catenin pathway is downregulated, and when Wnt/ß-catenin signaling is activated in osteocytes, dendrite development is suppressed and the expression of dentin matrix protein 1 (DMP1) is inhibited. Aberrant activation of Wnt/ß-catenin signaling in osteocytes leads to the spontaneous deposition of extra-large mineralized nodules on the surface of collagen fibrils. The altered mineral crystal structure and decreased bonding force between minerals and the organic matrix indicate the inferior integration of minerals and collagen. In conclusion, Wnt/ß-catenin signaling plays a critical role in the terminal differentiation of osteocytes and as such, targeting Wnt/ß-catenin signaling in osteocytes may serve as a potential therapeutic approach for the management of bone-related diseases.

Target screening analysis of 970 semi-volatile organic compounds adsorbed on atmospheric particulate matter in Hanoi, Vietnam.

Vietnam's rapid economic development has resulted in dramatic increases in construction and the number of transportation vehicles. There is now growing public concern regarding increasing air pollution, especially in big cities; however, little information is available on air quality, particularly regarding semi-volatile organic compounds (SVOCs) adsorbed on atmospheric particulate matter. Here, we determined the frequency and concentrations of 970 SVOCs in 48 air particle samples collected by means of high-volume air sampling in Hanoi, Vietnam, by using a target screening method and a gas chromatography-mass spectrometry database. A total of 118 compounds (12.2% of the target compounds) were detected at least once in the samples, and the number of chemicals detected in each sample ranged from 85 to 103 (median, 92). For samples collected near a heavily trafficked road, the concentrations of target compounds in the samples were higher in samples collected during the day than in those collected at night, whereas the opposite was true for samples collected in a highly populated residential area with industrial activities related to the production of fresh noodles. Sixteen PAHs were detected at high concentrations in nearly 100% of the samples. Eighteen pesticides were detected, with permethrin being detected the most frequently (>70% samples), which can be explained by the use of permethrin-based Permecide 50 EC for dengue fever control during the sampling period. Endocrine-disrupting chemicals (i.e., bisphenol A, 4-nitrophenol) and pharmaceuticals and personal care products (diethyltoluamide, caffeine) were detected in over 90% of the samples. Seven sterols, five phthalate compounds and five organophosphorus flame retardants were detected in the samples. This is the first comprehensive survey of SVOCs adsorbed on atmospheric particulate matter in Vietnam, and as such, this study provides important new information about the frequency and concentrations of atmospheric SVOC contamination. The variety of chemicals detected in this study implies an abundance of pollution sources; further investigations to determine these pollution sources and the risks posed by the detected SVOCs to human health are warranted.

Effect of Substrate Stiffness on Mechanical Coupling and Force Propagation at the Infarct Boundary.

Heterogeneous intercellular coupling plays a significant role in mechanical and electrical signal transmission in the heart. Although many studies have investigated the electrical signal conduction between myocytes and nonmyocytes within the heart muscle tissue, there are not many that have looked into the mechanical counterpart. This study aims to investigate the effect of substrate stiffness and the presence of cardiac myofibroblasts (CMFs) on mechanical force propagation across cardiomyocytes (CMs) and CMFs in healthy and heart-attack-mimicking matrix stiffness conditions. The contractile forces generated by the CMs and their propagation across the CMFs were measured using a bio-nanoindenter integrated with fluorescence microscopy for fast calcium imaging. Our results showed that softer substrates facilitated stronger and further signal transmission. Interestingly, the presence of the CMFs attenuated the signal propagation in a stiffness-dependent manner. Stiffer substrates with CMFs present attenuated the signal ∼24-32% more compared to soft substrates with CMFs, indicating a synergistic detrimental effect of increased matrix stiffness and increased CMF numbers after myocardial infarction on myocardial function. Furthermore, the beating pattern of the CMF movement at the CM-CMF boundary also depended on the substrate stiffness, thereby influencing the waveform of the propagation of CM-generated contractile forces. We performed computer simulations to further understand the occurrence of different force transmission patterns and showed that cell-matrix focal adhesions assembled at the CM-CMF interfaces, which differs depending on the substrates stiffness, play important roles in determining the efficiency and mechanism of signal transmission. In conclusion, in addition to substrate stiffness, the degree and type of cell-cell and cell-matrix interactions, affected by the substrate stiffness, influence mechanical signal conduction between myocytes and nonmyocytes in the heart muscle tissue.