Results from regression model.

∧<p>adjusted for age, gender and previous trauma.</p

Study population characteristics stratified by the status.

*<p>Mean (SD). OAT: oral anticoagulant therapy.</p

Results from regression model.

∧<p>adjusted for age, gender and previous trauma.</p

Results from regression model – effect of drug classes.

<p>OAT: oral anticoagulant therapy; ^∧adjusted for age, gender and previous trauma.</p

Results from conditional regression model stratified by history of recent trauma.

<p>Results from conditional regression model stratified by history of recent trauma.</p

Image1_The NFATc1/P2X7 receptor relationship in human intervertebral disc cells.TIF

A comprehensive understanding of the molecules that play key roles in the physiological and pathological homeostasis of the human intervertebral disc (IVD) remains challenging, as does the development of new therapeutic treatments. We recently found a positive correlation between IVD degeneration (IDD) and P2X7 receptor (P2X7R) expression increases both in the cytoplasm and in the nucleus. Using immunocytochemistry, reverse transcription PCR (RT-PCR), overexpression, and chromatin immunoprecipitation, we found that NFATc1 and hypoxia-inducible factor-1α (HIF-1α) are critical regulators of P2X7R. Both transcription factors are recruited at the promoter of the P2RX7 gene and involved in its positive and negative regulation, respectively. Furthermore, using the proximity ligation assay, we revealed that P2X7R and NFATc1 form a molecular complex and that P2X7R is closely associated with lamin A/C, a major component of the nuclear lamina. Collectively, our study identifies, for the first time, P2X7R and NFATc1 as markers of IVD degeneration and demonstrates that both NFATc1 and lamin A/C are interaction partners of P2X7R.</p

Image2_The NFATc1/P2X7 receptor relationship in human intervertebral disc cells.TIF

A comprehensive understanding of the molecules that play key roles in the physiological and pathological homeostasis of the human intervertebral disc (IVD) remains challenging, as does the development of new therapeutic treatments. We recently found a positive correlation between IVD degeneration (IDD) and P2X7 receptor (P2X7R) expression increases both in the cytoplasm and in the nucleus. Using immunocytochemistry, reverse transcription PCR (RT-PCR), overexpression, and chromatin immunoprecipitation, we found that NFATc1 and hypoxia-inducible factor-1α (HIF-1α) are critical regulators of P2X7R. Both transcription factors are recruited at the promoter of the P2RX7 gene and involved in its positive and negative regulation, respectively. Furthermore, using the proximity ligation assay, we revealed that P2X7R and NFATc1 form a molecular complex and that P2X7R is closely associated with lamin A/C, a major component of the nuclear lamina. Collectively, our study identifies, for the first time, P2X7R and NFATc1 as markers of IVD degeneration and demonstrates that both NFATc1 and lamin A/C are interaction partners of P2X7R.</p

Selection of the genes significantly different between ET and BAT with a 10<i>-</i>fold difference in expression levels.

<p>Selection of the genes significantly different between ET and BAT with a 10<i>-</i>fold difference in expression levels.</p

Primer sequences.

<p>Primer sequences.</p

Consistent anomalies observed in ET and BAT by a-CGH.

*<p>further amplification in ET, with respect to BAT.</p><p>In bold: anomalies limited to ETs.</p><p>In square bracket: genomic positions (according to NCBI 36 build) of the observed anomalies.</p><p>In round brackets: mosaicism degree of the observed anomaly. The percentage of abnormal cells was inferred using the formula proposed by Valli et al. That formula cannot be applied to the amplified segments (EGFR, CDK4, MDM2 and 15q24.1) since their ploidy status is unknown.</p