540 Chemie und zugeordnete Wissenschaften
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Extracellular vesicles
(2021)
Osteoporosis is characterized by low bone mass and damage to the bone tissue’s microarchitecture, leading to increased fracture risk. Several studies have provided evidence for associations between psychosocial stress and osteoporosis through various pathways, including the hypothalamic-pituitary-adrenocortical axis, the sympathetic nervous system, and other endocrine factors. As psychosocial stress provokes oxidative cellular stress with consequences for mitochondrial function and cell signaling (e.g., gene expression, inflammation), it is of interest whether extracellular vesicles (EVs) may be a relevant biomarker in this context or act by transporting substances. EVs are intercellular communicators, transfer substances encapsulated in them, modify the phenotype and function of target cells, mediate cell-cell communication, and, therefore, have critical applications in disease progression and clinical diagnosis and therapy. This review summarizes the characteristics of EVs, their role in stress and osteoporosis, and their benefit as biological markers. We demonstrate that EVs are potential mediators of psychosocial stress and osteoporosis and may be beneficial in innovative research settings.
Background Previous studies found evidence that dispositional optimism is related to lower pain sensitivity. Recent findings suggest that temporarily increasing optimism by means of imagining a positive future may also have pain-alleviating effects. Objectives The present experiment was designed to investigate conditioned pain modulation (CPM) as a potential underlying mechanism of this pain-alleviating effect of induced optimism. Methods For this purpose, 45 healthy participants were randomized into an optimistic or neutral imagery condition. Additionally, participants completed questionnaires on dispositional optimism, pain catastrophizing and pain expectations. CPM was assessed by delivering a series of five heat pain stimuli on the nondominant hand before and during immersion of the dominant hand in water of 5 degrees C for 70 s. Results A clear CPM effect was found, that is heat pain reports were lower during simultaneous cold water stimulation. Although the optimism manipulation successfully increased optimism, it did not affect pain ratings or CPM. Post hoc analyses indicated that dispositional optimism was not associated with the magnitude of CPM, but pain catastrophizing and pain expectations did significantly correlate with the CPM effect. Conclusion Pain-specific but not general cognitions appear to influence endogenous pain modulation. Significance Conditioned pain modulation is not the underlying mechanism of the pain-alleviating effects of induced optimism. However, pain-specific cognitions including pain catastrophizing and pain expectations affect endogenous pain modulation which should be taken into account in treatment and CPM research.
Intervertebral disc (IVD) cells are naturally exposed to high osmolarity and complex mechanical loading, which drive microenvironmental osmotic changes. Age- and degeneration-induced degradation of the IVD's extracellular matrix causes osmotic imbalance, which, together with an altered function of cellular receptors and signalling pathways, instigates local osmotic stress. Cellular responses to osmotic stress include osmoadaptation and activation of pro-inflammatory pathways. This review summarises the current knowledge on how IVD cells sense local osmotic changes and translate these signals into physiological or pathophysiological responses, with a focus on inflammation. Furthermore, it discusses the expression and function of putative membrane osmosensors (e.g. solute carrier transporters, transient receptor potential channels, aquaporins and acid-sensing ion channels) and osmosignalling mediators [e.g. tonicity responseelement-binding protein/nuclear factor of activated T-cells 5 (TonEBP/NFAT5), nuclear factor kappa-lightchain-enhancer of activated B cells (NF-kappa B)] in healthy and degenerated IVDs. Finally, an overview of the potential therapeutic targets for modifying osmosensing and osmosignalling in degenerated IVDs is provided.