Pulsed electromagnetic fields (PEMF) can be used to treat bone-related diseases, but the underlying mechanism remains unclear, especially the process by which PEMFs initiate biological effects. In this study, we demonstrated the effects of PEMF on proliferation and differentiation of osteoblasts using the model of calcium transients induced by high extracellular calcium. Our results showed that PEMF can increase both the percentage of responding cells and amplitude of intracellular calcium transients induced by high extracellular calcium stimulation. Compared with corresponding extracellular calcium levels, PEMF stimulation increased proliferation and differentiation of osteoblasts and related gene expressions, such as insulin-like growth factor 1 (IGF-1), alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and osteocalcin (OCN), which can be completely abolished by BAPTA-AM. Moreover, PEMF did not affect proliferation and differentiation of osteoblasts if no intracellular calcium transient was present in osteoblasts during PEMF exposure. Our results revealed that PEMF affects osteoblast proliferation and differentiation through enhanced intracellular calcium transients, which provided a cue to treat bone-related diseases with PEMF. Bioelectromagnetics. 38:541-549, 2017. © 2017 Wiley Periodicals, Inc.
Numerous studies have demonstrated that fluid shear stress (FSS) may promote the proliferation and differentiation of osteoblast cells. However, proliferation and differentiation are mutually exclusive processes and are unlikely to be promoted by FSS simultaneously. Cell proliferation and differentiation induced by FSS has rarely been reported. In order to provide an insight into this process, the present study investigated the effects of FSS on osteoblast-like MC3T3 cells in the G0/G1 phase, the period during which the fate of a cell is determined. The results of the present study demonstrated that FSS promoted alkaline phosphatase (ALP) activity, and the mRNA expression and protein expression of osteocalcin, collagen type I and runt-related transcription factor 2 (Runx2), while inhibiting DNA synthesis and arresting the cell cycle at the G0/G1 phase. The increase in Runx2 and ALP activity was accompanied by the activation of calcium/calmodulin-dependent protein kinase type II (CaMK II) and extracellular signal-regulated kinases 1/2 (ERK1/2), which was completely abolished by treatment with KN93 and U0126, respectively. In addition, the inhibition of ERK1/2, although not CaMK II, decreased p21Cip/Kip activity, resulting in an increase in cell number and S phase re-entry. The results of the present study indicated that in the G0/G1 phase, FSS promoted osteoblast differentiation via the CaMK II and ERK1/2 signaling pathways, and blocked the cell cycle at the G0/G1 phase via the ERK1/2 pathway only. The present findings provided an increased understanding of osteoblastic mechanobiology.
Microfluidics attracts much attention due to its multiple advantages such as high throughput, rapid analysis, low sample volume, and high sensitivity. Microfluidics has profoundly influenced many fields including chemistry, biology, medicine, information technology, and other disciplines. However, some stumbling stones (miniaturization, integration, and intelligence) strain the development of industrialization and commercialization of microchips. The miniaturization of microfluidics means fewer samples and reagents, shorter times to results, and less footprint space consumption, enabling a high throughput and parallelism of sample analysis. Additionally, micro-size channels tend to produce laminar flow, which probably permits some creative applications that are not accessible to traditional fluid-processing platforms. The reasonable integration of biomedical/physical biosensors, semiconductor microelectronics, communications, and other cutting-edge technologies should greatly expand the applications of current microfluidic devices and help develop the next generation of lab-on-a-chip (LOC). At the same time, the evolution of artificial intelligence also gives another strong impetus to the rapid development of microfluidics. Biomedical applications based on microfluidics normally bring a large amount of complex data, so it is a big challenge for researchers and technicians to analyze those huge and complicated data accurately and quickly. To address this problem, machine learning is viewed as an indispensable and powerful tool in processing the data collected from micro-devices. In this review, we mainly focus on discussing the integration, miniaturization, portability, and intelligence of microfluidics technology.
Currently, many microchips must rely on an external force (such as syringe pump, electro-hydrodynamic pump, and peristaltic pump, etc.) to control the solution in the microchannels, which probably adds manual operating errors, affects the accuracy of fluid manipulation, and enlarges the noise of signal. In addition, the reasonable integration of micropump and microchip remain the stumbling block for the commercialization of microfluidic technique. To solve those two problems, we designed and fabricated a thermal bubble micropump based on MEMS (micro-electro-mechanical systems) technique. Many parameters (voltage, pulse time, cycle delay time, etc.) affecting the performance of this micropump were explored in this work. The experimental results showed the flow rate of solution with the assistance of a micropump reached more than 15 μL/min in the optimal condition. Finally, a method about measuring total aflatoxin in Chinese herbs was successfully developed based on the integrated platform contained competitive immunoassay and our micropump-based microfluidics. Additionally, the limit of detection in quantifying total aflatoxin (AF) was 0.0615 pg/mL in this platform. The data indicate this combined technique of biochemical assays and micropump based microchip have huge potential in automatically, rapidly, and sensitively measuring other low concentration of biochemical samples with small volume.
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