Interstitial fluid flow and associated shear stress are relevant mechanical signals in cartilage and bone (patho)physiology. However, their effects on chondrosarcoma cell motility, invasion and metastasis have yet to be delineated. Using human SW1353, HS.819.T and CH2879 chondrosarcoma cell lines as model systems, we found that fluid shear stress induces the accumulation of cyclic AMP (cAMP) and interleukin-1β (IL-1β), which in turn markedly enhance chondrosarcoma cell motility and invasion via the induction of matrix metalloproteinase-7 (MMP-7). Specifically, shear-induced cAMP and IL-1β activate PI3-K, ERK1/2 and p38 signaling pathways, which lead to the synthesis of MMP-7 via transactivating NF-κB and c-Jun in human chondrosarcoma cells. Importantly, MMP-7 upregulation in response to shear stress exposure has the ability to promote lung colonization of chondrosarcomas in vivo. These findings offer a better understanding of the mechanisms underlying MMP-7 activation in shear-stimulated chondrosarcoma cells, and provide insights on designing new therapeutic strategies to interfere with chondrosarcoma invasion and metastasis.

Matrix metalloproteinase-1 (MMP-1) is a potential biomarker for chondrosarcoma that is overexpressed at the invading edges of articular cartilage, and its expression correlates with poor survival rates. However, the molecular mechanisms of MMP-1 regulation and its potential contribution to chondrosarcoma cell invasion have yet to be elucidated, especially in shear-activated cells. Using molecular biology tools and an in vitro fluid shear model, we report that shear stress upregulates cyclic AMP (cAMP) and interleukin-1β (IL-1β) release, which in turn promotes the invasion of chondrosarcoma cells via the induction of MMP-1 in a phosphoinositide 3-kinase (PI3-K)- and ERK1/2-dependent manner. Activated PI3-K and ERK1/2 signaling pathways phosphorylate c-Jun, which in turn transactivates MMP-1 in human chondrosarcoma cells. Collectively, fluid shear stress upregulates matrix MMP-1 expression, which is responsible for the enhanced invasion of human chondrosarcoma cells.

Background Accumulation of alpha-synuclein (α-syn) is a main pathological hallmark of Parkinson’s and related diseases, which are collectively known as synucleinopathies. Growing evidence has supported that the same protein can induce remarkably distinct pathological progresses and disease phenotypes, suggesting the existence of strain difference among α-syn fibrils. Previous studies have shown that α-syn pathology can propagate from the peripheral nervous system (PNS) to the central nervous system (CNS) in a “prion-like” manner. However, the difference of the propagation potency from the periphery to CNS among different α-syn strains remains unknown and the effect of different generation processes of these strains on the potency of seeding and propagation remains to be revealed in more detail. Methods Three strains of preformed α-syn fibrils (PFFs) were generated in different buffer conditions which varied in pH and ionic concentrations. The α-syn PFFs were intramuscularly (IM) injected into a novel bacterial artificial chromosome (BAC) transgenic mouse line that expresses wild-type human α-syn, and the efficiency of seeding and propagation of these PFFs from the PNS to the CNS was evaluated. Results The three strains of α-syn PFFs triggered distinct propagation patterns. The fibrils generated in mildly acidic buffer led to the most severe α-syn pathology, degeneration of motor neurons and microgliosis in the spinal cord. Conclusions The different α-syn conformers generated in different conditions exhibited strain-specific pathology and propagation patterns from the periphery to the CNS, which further supports the view that α-syn strains may be responsible for the heterogeneity of pathological features and disease progresses among synucleinopathies.

Abstract. As an abstract concept, 'location error' in is considered to be an important element with great difficult to understand and apply. The paper designs and develops an instrument to measure the location error. The location error is affected by different position methods and reference selection. So we choose position element by rotating the disk. The tiny movement transfers by grating ruler and programming by PLC can show the error on text display, which also helps students understand the position principle and related concepts of location error. After comparing measurement results with theoretical calculations and analyzing the measurement accuracy, the paper draws a conclusion that the teaching aid owns reliability and a promotion of high value.