Tumor Necrosis Factor-α– and Interleukin-1β–Dependent Matrix Metalloproteinase-3 Expression in Nucleus Pulposus Cells Requires Cooperative Signaling via Syndecan 4 and Mitogen-Activated Protein Kinase–NF-κB Axis Implications in Inflammatory Disc Disease

Matrix metalloproteinase-3 (MMP-3) plays an important role in intervertebral disc degeneration, a ubiquitous condition closely linked to low back pain and disability. Elevated expression of syndecan 4, a cell surface heparan sulfate proteoglycan, actively controls disc matrix catabolism. However, the relationship between MMP-3 expression and syndecan 4 in the context of inflammatory disc disease has not been clearly defined. We investigated the mechanisms by which cytokines control MMP-3 expression in rat and human nucleus pulposus cells. Cytokine treatment increased MMP-3 expression and promoter activity. Stable silencing of syndecan 4 blocked cytokine-mediated MMP-3 expression; more important, syndecan 4 did not mediate its effects through NF-κB or mitogen-activated protein kinase (MAPK) pathways. However, treatment with MAPK and NF-κB inhibitors resulted in partial blocking of the inductive effect of cytokines on MMP-3 expression. Loss-of-function studies confirmed that NF-κB, p38α/β2/γ/δ, and extracellular signal–regulated kinase (ERK) 2, but not ERK1, contributed to cytokine-dependent induction of MMP3 promoter activity. Similarly, inhibitor treatments, lentiviral short hairpin-p65, and short hairpin-IκB kinase β significantly decreased cytokine-dependent up-regulation in MMP-3 expression. Finally, we show that transforming growth factor-β can block the up-regulation of MMP-3 induced by tumor necrosis factor (TNF)-α by counteracting the NF-κB pathway and syndecan 4 expression. Taken together, our results suggest that cooperative signaling through syndecan 4 and the TNF receptor 1–MAPK–NF-κB axis is required for TNF-α–dependent expression of MMP-3 in nucleus pulposus cells. Controlling these pathways may slow the progression of intervertebral disc degeneration and matrix catabolism

Combination of Acellular Nerve Graft and Schwann Cells-Like Cells for Rat Sciatic Nerve Regeneration

Objective. To investigate the effect of tissue engineering nerve on repair of rat sciatic nerve defect. Methods. Forty-five rats with defective sciatic nerve were randomly divided into three groups. Rats in group A were repaired by acellular nerve grafts only. Rats in group B were repaired by tissue engineering nerve. In group C, rats were repaired by autogenous nerve grafts. After six and twelve weeks, sciatic nerve functional index (SFI), neural electrophysiology (NEP), histological and transmission electron microscope observation, recovery ratio of wet weight of gastrocnemius muscle, regenerated myelinated nerve fibers number, nerve fiber diameter, and thickness of the myelin sheath were measured to assess the effect. Results. After six and twelve weeks, the recovery ratio of SFI and wet weight of gastrocnemius muscle, NEP, and the result of regenerated myelinated nerve fibers in groups B and C were superior to that of group A (P<0.05), and the difference between groups B and C was not statistically significant (P>0.05). Conclusion. The tissue engineering nerve composed of acellular allogenic nerve scaffold and Schwann cells-like cells can effectively repair the nerve defect in rats and its effect was similar to that of the autogenous nerve grafts