In chondrocytes SOX9 gene expression
VEGFR inhibitor is regulated by osmotic loading. Here we characterise SOX9 mRNA regulation through static and cyclical application of hyperosmotic conditions in normal and OA monolayer equine chondrocytes. Furthermore, we investigate whether extracellular signal-regulated protein kinase (ERK)1/2 mitogen-activated protein kinases (MAPK) pathways have a role in this regulation of SOX9.
Methods: Equine chondrocytes harvested from normal or OA joints were subjected to different osmotic loading patterns as either primary (PO) or passaged (P2) cells. The involvement of MEK-ERK signalling was demonstrated by using pharmacological inhibitors. In addition SOX9 gene stability was determined. Levels of transcripts encoding SOX9, Col2A1 and aggrecan were measured using qRT-PCR. De novo glycosaminoglycan synthesis of explants was determined with (35)S sulphate during static hyperosmolar loading.
Results: MEK-ERK signalling increases glycosaminoglycans (GAG) synthesis in explants.
Static hyperosmotic conditions significantly reduced SOX9 mRNA in normal Epigenetics inhibitor P2 and OA PO but not normal PO chondrocytes. SOX9 mRNA was stabilised by hyperosmotic conditions. Cyclical loading of normal P2 and OA PO but not normal PO cells led to an increase in SOX9 gene expression and this was prevented by MEK1/2 inhibition.
Conclusions: The response to osmotic loading of SOX9 mRNA is dependent on the nature of the osmotic stimulation and the chondrocyte phenotype. This variation may be important in disease progression. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.”
“An increased R2 recovery component of the blink reflex (R2-BRrc) has been observed in
Parkinson’s AZD2014 concentration disease (PD), cranio-cervical dystonia, dystonic tremor and essential tremor with associated resting tremor (rET), while the BRrc was reported normal in patients with essential tremor (ET). Distinguishing rET from tremor dominant PD (tPD) may be challenging especially in the first stages of the diseases, in the absence of DAT-SPECT investigation. We evaluated the possible usefulness of BRrc for differentiating subjects with de novo tPD from those with rET. We investigated R2-BRrc at interstimulus intervals (ISI) of 100, 150, 200, 300, 400, 500 and 750 ms in 11 participants with tPD, 10 with rET and 20 healthy controls. All participants underwent DAT-SPECT and cardiac MIBG scintigraphy.
R2 recovery was significantly enhanced in tPD compared to controls at all investigated ISIs (p < 0.001), while in subjects with rET patients BRrc was significantly increased compared to controls at ISI 150, 200, 300, 400, 500 and 750 ms (p < 0.001).
At ISI 100 R2-BRrc distinguished patients participants with de novo tPD from those with rET with a sensitivity, specificity and accuracy of 100%. Our findings demonstrate the usefulness of BRrc for differentiating de novo tPD from rET. (C) 2013 Elsevier Ltd.