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The results of this study indicate that HIZ may be a specific signal for the inflammatory reaction of painful intervertebral disc.

Aim: Sirtuin 1 (Sirt1) is the class III histone/protein deacetylase that interferes with the NF-κB signaling pathway, thereby has antiinflammatory function. This study was undertaken to investigate whether Sirt1 could protect osteoblasts against TNF-α-induced injury in vitro. Methods: Murine osteoblastic cell line, MC3T3-E1, was used. Overexpress of Sirt1 protein in MC3T3-E1 cells was made by transfection the cells with Sirt1-overexpressing adenovirus. The levels of mRNAs and proteins were determined with qRT-PCR and Western blotting, respectively. The activity of NF-κB was examined using NF-κB luciferase assay. The NO concentration was measured using the Griess method. Results: Treatment of MC3T3-E1 cells with TNF-α (2.5-10 ng/mL) suppressed Sirt1 protein expression in a concentration-dependent manner. TNF-α (5 ng/mL) resulted in an increase in apoptosis and a reduction in ALP activity in the cells. Overexpression of Sirt1 in the cells significantly attenuated TNF-α-induced injury through suppressing apoptosis, increasing ALP activity, and increasing the expression of Runx2 and osteocalcin mRNAs. Furthermore, overexpression of Sirt1 in the cells significantly suppressed TNF-α-induced NF-κB activation, followed by reducing the expression of iNOS and NO formation. Sirt1 activator resveratrol (10 µmol/L) mimicked the protection of the cells by Sirt1 overexpression against TNF-α-induced injury, which was reversed by the Sirt1 inhibitor EX-527 (5 µmol/L). Conclusion: Overexpression of Sirt1 protects MC3T3-E1 osteoblasts aganst TNF-α-induced cell injury in vitro, at least in part, via suppressing NF-κB signaling. Sirt1 may be a novel therapeutic target for treating rheumatoid arthritis-related bone loss.

Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, have been used clinically as a cholesterol-lowering drug to treat hyperlipidemia. In recent years, accumulating evidence indicates the possible beneficial effect of statins on osteoporosis. However, the underlying molecular mechanism remains to be elucidated. In the present study, we investigated the therapeutic effects of simvastatin on cell viability, apoptosis, and alkaline phosphatase activity in murine osteoblastic MC3T3-E1 cells treated by hydrogen peroxide (H(2)O(2), 100 μM). It was shown that simvastatin suppressed H(2)O(2)-induced oxidative stress and attenuated H(2)O(2)-induced cell injury including increasing osteoblastic viability, inhibiting apoptosis, and promoting differentiation. Then, we examined the effects of simvastatin (10(-7) M) on Nox1, Nox2, and Nox4 expressions in osteoblastic cells treated by H(2)O(2) (100 μM). We found that in MC3T3-E1 cells, H(2)O(2)-induced upregulation of Nox4 expression was inhibited by simvastatin, which was restored by farnesyl pyrophosphate (5 μM) as well as geranylgeranyl pyrophosphate (5 μM). RNAi approach was used to reduce Nox4 protein levels in osteoblastic cells to explore its biological effects against H(2)O(2)-induced oxidative damage. When Nox4 expression was reduced in osteoblastic cells, H(2)O(2)-induced cell injury was attenuated markedly. We concluded that simvastatin protected osteoblast against H(2)O(2)-induced oxidative damage, at least in part, via inhibiting the upregulation of Nox4.

We believe this is the first case of cervical myelopathy caused by simultaneous anomalies at the level of atlas involving hypoplasia of the posterior arch of the atlas, partial ossification of the transverse atlantal ligament, and hypertrophy of the dens. Surgical intervention improved the neurologic impairment.

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BrdU injection into the central region of sheep discs resulted in degeneration of intervertebral discs. This progressive, degenerative process was confirmed using MRI, histology, and by observing changes in biochemistry. Degeneration occurred in a manner that was similar to that observed in human disc degeneration.