Effects of puerarin on the intervertebral disc degeneration and biological characteristics of nucleus pulposus cells.

CONTEXT: Intervertebral disc degeneration (IDD) is the pathological basis of spinal degenerative diseases. Puerarin (PU) is an isoflavonoid with functions and medicinal properties. OBJECTIVE: To explore the effect of PU on IDD and its potential mechanism of action. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were divided into sham, IDD, low PU, and high PU groups. Rat nucleus pulposus cells (NPCs) were isolated and divided into control, IL-1ß, 100 and 200 µmol/mL PU, TAK-242 (TLR4 inhibitor), or 200 µmol/mL PU + LPS (TLR4 activator) groups. The water content, inflammatory factors, proliferation activity, TLR4/NF-κB pathway activity, apoptosis rate, protein expression of apoptosis, and histology of the extracellular matrix (ECM) were analysed. RESULTS: In vivo: Compared with the IDD group, disorganization of intervertebral disc tissue was significantly improved, water content (2.80 ± 0.24 mg, 3.91 ± 0.31 mg vs. 2.02 ± 0.21 mg) and expression levels of collagen II and aggrecan were significantly increased, and the levels of inflammatory factors and the expression levels of TLR4, MyD88, and p-p65 were significantly decreased in IDD rats treated with PU. In vitro: Compared with the IL-1ß group, the proliferation activity of IL-1ß-treated NPCs and the expression of collagen II and aggrecan were significantly increased, while the apoptosis rate, levels of inflammatory factors, and the expression levels of TLR4, MyD88, and p-p65 were significantly decreased in IL-1ß-treated NPCs treated with PU. LPS reversed the biological function changes of IL-1ß-treated NPCs induced by PU. CONCLUSIONS: PU can delay the progression of IDD by inhibiting activation of the TLR4/NF-κB pathway.

The effect of IL-1R1 and IL-1RN polymorphisms on osteoporosis predisposition in a Chinese Han population.

BACKGROUND: Osteoporosis (OP) is a common inflammatory disease. The goal of this study was to investigate the effect of IL-1R1 and IL-1RN polymorphisms on OP predisposition among the Chinese Han population. METHODS: Six single nucleotide polymorphisms (SNPs) in IL-1R1 and IL-1RN were genotyped using the Agena MassARRAY platform in 594 OP patients and 599 age- and sex- matched healthy controls. Logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Multifactor dimensionality reduction (MDR) analysis was used to analyze SNP-SNP interaction. The correlations of genotypes with clinical variables were evaluated using analysis of covariance (ANOVA). RESULTS: Overall, IL-1R1 rs3917225 (OR = 1.40, 95% CI: 1.10-1.80, p = 0.007) was associated with a higher risk for OP, while IL-1RN rs17042888 (OR = 0.55, 95% CI: 0.34-0.90, p = 0.016) was associated with a lower risk. Specifically, the risk association between these polymorphisms and OP risk might be related to age, sex and BMI. Furthermore, rs10490571, rs17042888, rs3181052 and rs452204 were associated with the T scores of the lumbar spine or total hip. CONCLUSION: This study is the first to find that rs10490571, rs956730 and rs3917225 in IL-1R1 and rs17042888 in IL-1RN may be genetic contributors to OP susceptibility among the Chinese Han population. Our findings increase the understanding of the role of IL-1R1 and IL-1RN in the genetic etiology of osteoporosis. Nevertheless, these results should be confirmed in larger cohorts.