scholarly journals Early OA Stage Like Response Occurs after Dynamic Stretching of Human Synovial Fibroblasts

2020 ◽  
Vol 21 (11) ◽  
pp. 3874
Author(s):  
Ute Nazet ◽  
Susanne Grässel ◽  
Jonathan Jantsch ◽  
Peter Proff ◽  
Agnes Schröder ◽  
...  

As events triggering early osteoarthritis onset can be related to mechanical stress and proinflammatory signaling, we investigated the effect of different mechanical strain protocols on the expression of proinflammatory genes, as well as extracellular matrix remodelling in human synovial fibroblasts. Three distinct models of tensile stretching were applied: static isotropic tensile strain at 0 Hz, 16% tension for 48 h; short-term high-frequency cyclic tension at 1 Hz, 10% tension for 4 h; and dynamic tensile stretching for 48 h, consisting of two blocks of moderate stretching at 0.2 Hz, 2%, advanced stretching at 0.5 Hz, 15%, or a combination of both. General signs of inflammation were present after static isotropic tension, whereas short-term high-frequency cyclic tension showed increased levels of IL-6 paired with diminished levels of IL-1β. Reduced inflammatory effects of TNF-α, IL-6, and IL-1β were observed when exposed to advanced stretching. Long-term tensile strain induced extracellular matrix remodelling at the gene and protein levels. While hyaluronan acid synthesis was increased with static tensile strain, dynamic tensile stretching had a reducing effect. Our study revealed that proinflammatory markers were activated by mechanical strain as seen in static isotropic tension and short-term high-frequency tensile strain, whereas long-term exposure induced extracellular matrix remodelling processes.

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 298
Author(s):  
Ute Nazet ◽  
Laura Feulner ◽  
Dominique Muschter ◽  
Patrick Neubert ◽  
Valentin Schatz ◽  
...  

Genetic predisposition, traumatic events, or excessive mechanical exposure provoke arthritic changes in the temporomandibular joint (TMJ). We analysed the impact of mechanical stress that might be involved in the development and progression of TMJ osteoarthritis (OA) on murine synovial fibroblasts (SFs) of temporomandibular origin. SFs were subjected to different protocols of mechanical stress, either to a high-frequency tensile strain for 4 h or to a tensile strain of varying magnitude for 48 h. The TMJ OA induction was evaluated based on the gene and protein secretion of inflammatory factors (Icam-1, Cxcl-1, Cxcl-2, Il-1ß, Il-1ra, Il-6, Ptgs-2, PG-E2), subchondral bone remodelling (Rankl, Opg), and extracellular matrix components (Col1a2, Has-1, collagen and hyaluronic acid deposition) using RT-qPCR, ELISA, and HPLC. A short high-frequency tensile strain had only minor effects on inflammatory factors and no effects on the subchondral bone remodelling induction or matrix constituent production. A prolonged tensile strain of moderate and advanced magnitude increased the expression of inflammatory factors. An advanced tensile strain enhanced the Ptgs-2 and PG-E2 expression, while the expression of further inflammatory factors were decreased. The tensile strain protocols had no effects on the RANKL/OPG expression, while the advanced tensile strain significantly reduced the deposition of matrix constituent contents of collagen and hyaluronic acid. The data indicates that the application of prolonged advanced mechanical stress on SFs promote PG-E2 protein secretion, while the deposition of extracellular matrix components is decreased.


1987 ◽  
Vol 27 (4) ◽  
pp. 283-287 ◽  
Author(s):  
Prasad R. Palakurthy ◽  
Claudio Maldonado ◽  
Gurbachan Sohi ◽  
Nancy C. Flowers

2021 ◽  
Vol 12 ◽  
Author(s):  
Kang Chen ◽  
Yang Huang ◽  
Chunni Liu ◽  
Yu Liang ◽  
Maoteng Li

Long non-coding RNAs (lncRNAs) play an important role in the response of plants to drought stress. The previous studies have reported that overexpression of LEA3 and VOC could enhance drought tolerance and improve the oil content in Brassica napus and Arabidopsis thaliana, and most of the efforts have been invested in the gene function analysis, there is little understanding of how genes that involved in these important pathways are regulated. In the present study, the transcriptomic results of LEA3 and VOC over-expressed (OE) lines were compared with the RNAi lines, mutant lines and control lines under long-term and short-term drought treatment, a series of differentially expressed lncRNAs were identified, and their regulation patterns in mRNA were also investigated in above mentioned materials. The regulation of the target genes of differentially expressed lncRNAs on plant biological functions was studied. It was revealed that the mutant lines had less drought-response related lncRNAs than that of the OE lines. Functional analysis demonstrated that multiple genes were involved in the carbon-fixing and chlorophyll metabolism, such as CDR1, CHLM, and CH1, were regulated by the upregulated lncRNA in OE lines. In LEA-OE, AT4G13180 that promotes the fatty acid synthesis was regulated by five lncRNAs that were upregulated under both long-term and short-term drought treatments. The key genes, including of SHM1, GOX2, and GS2, in the methylglyoxal synthesis pathway were all regulated by a number of down-regulated lncRNAs in OE lines, thereby reducing the content of such harmful compounds produced under stress in plants. This study identified a series of lncRNAs related to the pathways that affect photosynthesis, chlorophyll synthesis, fatty acid synthesis, degradation, and other important effects on drought resistance and oil content. The present study provided a series of lncRNAs for further improvement of crop varieties, especially drought resistant and oil content traits.


Author(s):  
Nick Perham ◽  
Toni Howell ◽  
Andy Watt

AbstractFunding to support students with dyslexia in post-compulsory education is under pressure and more efficient assessments may offset some of this shortfall. We tested potential tasks for screening dyslexia: recall of adjective-noun, compared to noun-adjective, pairings (syntax) and recall of high versus low frequency letter pairings (bigrams). Students who reported themselves as dyslexic failed to show a normal syntax effect (greater recall of adjective-noun compared to noun-adjective pairings) and no significant difference in recall between the two types of bigrams whereas students who were not dyslexic showed the syntax effect and a bias towards recalling high frequency bigrams. Findings are consistent with recent explanations of dyslexia suggesting that those affected find it difficult to learn and utilise sequential long-term order information (Szmalec et al. Journal of Experimental Psychology: Learning, Memory & Cognition, 37(5) ,1270-1279, 2011). Further, ROC curve analyses revealed both tasks showed acceptable diagnostic properties as they were able to discriminate between the two groups of participants.


2019 ◽  
Author(s):  
Eva Kimel ◽  
Atalia Hai Weiss ◽  
Hilla Jakoby ◽  
Luba Daikhin ◽  
Merav Ahissar

AbstractReduced short-term memory (STM) of individuals with dyslexia (IDDs) and enhanced STM of musicians are well documented, yet their causes are disputed. We hypothesized that their STMs reflect their sensitivities to accumulative long-term stimuli statistics. Indeed, when performing an STM task, IDDs had reduced benefit from syllable frequency, whereas musicians manifested an opposite effect, compared to controls. Interestingly, benefit from sequence-repetition did not significantly differ between groups, suggesting that it relies on different mechanisms. To test the generality of this separation across populations, we recruited a group of good-readers, whose native language contains a smaller fraction of the high-frequency syllables. Their span for these “high-frequency” syllables was small, yet their benefit from sequence-repetition was adequate. These experiments indicate that sensitivity to long-term stimuli distribution, and not to sequential repetition, is reduced in IDDs and enhanced in musicians, and this accounts for differences in their STM performance.


2014 ◽  
Vol 111 (4) ◽  
pp. 888-895 ◽  
Author(s):  
Michael Ryan ◽  
Jaime Kaminer ◽  
Patricia Enmore ◽  
Craig Evinger

Reflex blinks provide a model system for investigating motor learning in normal and pathological states. We investigated whether high-frequency stimulation (HFS) of the supraorbital branch of the trigeminal nerve before the R2 blink component (HFS-B) decreases reflex blink gain in alert rats. As with humans (Mao JB, Evinger C. J Neurosci 21: RC151, 2001), HFS-B significantly reduced blink size in the first hour after treatment for rats. Repeated days of HFS-B treatment produced long-term depression of blink circuits. Blink gain decreased exponentially across days, indicating a long-term depression of blink circuits. Additionally, the HFS-B protocol became more effective at depressing blink amplitude across days of treatment. This depression was not habituation, because neither long- nor short-term blink changes occurred when HFS was presented after the R2. To investigate whether gain modifications produced by HFS-B involved cerebellar networks, we trained rats in a delay eyelid conditioning paradigm using HFS-B as the unconditioned stimulus and a tone as the conditioned stimulus. As HFS-B depresses blink circuits and delay conditioning enhances blink circuit activity, occlusion should occur if they share neural networks. Rats acquiring robust eyelid conditioning did not exhibit decreases in blink gain, whereas rats developing low levels of eyelid conditioning exhibited weak, short-term reductions in blink gain. These results suggested that delay eyelid conditioning and long-term HFS-B utilize some of the same cerebellar circuits. The ability of repeated HFS-B treatment to depress trigeminal blink circuit activity long term implied that it may be a useful protocol to reduce hyperexcitable blink circuits that underlie diseases like benign essential blepharospasm.


2006 ◽  
Vol 95 (3) ◽  
pp. 1620-1629 ◽  
Author(s):  
Robert C. Froemke ◽  
Ishan A. Tsay ◽  
Mohamad Raad ◽  
John D. Long ◽  
Yang Dan

Long-term synaptic modification depends on the relative timing of individual pre- and postsynaptic spikes, but the rules governing the effects of multispike bursts remain to be fully understood. In particular, some studies suggest that the spike timing dependence of synaptic modification breaks down with high-frequency bursts. In this study, we characterized the effects of pre- and postsynaptic bursts on long-term modification of layer 2/3 synapses in visual cortical slices from young rats. We found that, while pairing-induced synaptic modification depends on the burst frequency, this dependence can be explained in terms of the timing of individual pre- and postsynaptic spikes. Later spikes in each burst are less effective in synaptic modification, but spike efficacy is regulated differently in pre- and postsynaptic bursts. Presynaptically, spike efficacy is progressively weakened, in parallel with short-term synaptic depression. Postsynaptically, spike efficacy is suppressed to a lesser extent, and it depends on postsynaptic potassium channel activation. Such timing-dependent interaction among multiple spikes can account for synaptic modifications induced by a variety of spike trains, including the frequency-dependent transition from depression to potentiation induced by a postsynaptic burst preceding a presynaptic burst.


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