Etiology for Degenerative Disc Disease

Degenerative disc disease is a multifaceted progressive irreversible condition and an inevitable part of aging,which has been found to be a contributing factor for low back pain and might cause radiculopathy,myelopathy,spinal stenosis,degenerative spondylolisthesis,and herniations.Its etiology is complex and multifactorial.Although genetics influence more dominant,the occupational and mechanical influences still persist as a major risk factor.This review emphasizes up-to-date knowledge regarding etiology of disc degeneration with special consideration on occupational,lifestyle factors,and genetic polymorphisms.

Adenovirus-mediated TGF-β1 gene transfer to human degenerative lumbar intervertebral disc cells

Objective To test the possibility of modification of human degenerative lumbar disc cells by the exogenous growth factor gene, transforming growth factor β_1 (TGF-β_ 1) cDNA, and the expression of the encoded protein. Methods Nucleus pulposus samples were surgically obtained from 8 patients with degenerat ive lumbar disc disease. The cells were cultured and directly infected by two a denoviral constructs, Ad/CMV-EGFP containing the enhanced green fluorecence pro tein (EGFP) gene (marker gene) and Ad/CMV-TGF-β_1 containing the potentially therapeutic TGF-β_1 gene. Transgene expression was analyzed by fluorescence production and immunohistochemical staining (Ad/CMV-TGF-β_1). Results Culture cells transducted by Ad/CMV-EGFP showed specific green fluorescence und er the fluoroscope and expression sustained for at least 4 weeks. When infe cted by Ad/CMV-TGF-β_1, approximally 30% of cultured cells were staind brown (+) with TGF-β_1 staining. Conclusion This study established the strategy of delivering a potentially therapeutic gene , TGF-β_1, by using an adenoviral vector to human degenerative lumbar interve rtebral disc cells.

Transplantation of gene-modified nucleus pulposus cells reverses rabbit intervertebral disc degeneration

Background Intervertebral disc degeneration is the main cause of low back pain. The purpose of this study was to explore potential methods for reversing the degeneration of lumbar intervertebral discs by transplantation of gene-modified nucleus pulposus cells into rabbit degenerative lumbar intervertebral discs after transfecting rabbit nucleus pulposus cells with adeno-associated virus 2 （AAV2）-mediated connective tissue growth factor （CTGF） and tissue inhibitor of metalloproteinases 1 （TIMP1） genes in vitro. Methods Computer tomography （CT）-guided percutaneous annulus fibrosus injury was performed to build degenerative lumbar intervertebral disc models in 60 New Zealand white rabbits, rAAV2-CTGF-IRES-TIMPI-transfected rabbit nucleus pulposus cells were transplanted into degenerative lumbar intervertebral discs （transplantation group）, phosphate-buffered saline （PBS） was injected into degenerative lumbar intervertebral discs （degeneration control group） and normal lumbar intervertebral discs served as a blank control group. After 6, 10 and 14 weeks, the disc height index （DHI） and signal intensity in intervertebral discs were observed by X-ray and magnetic resonance imaging （MRI） analysis The expression of CTGF and TIMP1 in nucleus pulposus tissue was determined by Western blotting analysis, the synthesis efficiency of proteoglycan was determined by a 35S-sulfate incorporation assay, and the mRNA expression of type II collagen and proteoglycan was detected by RT-PCR. Results MRI confirmed that degenerative intervertebral discs appeared two weeks after percutaneous puncture. Transgenic nucleus pulposus cell transplantation could retard the rapid deterioration of the DHI. MRI indicated that degenerative intervertebral discs were relieved in the transplantation group compared with the degeneration control group. The expression of collagen II mRNA and proteoglycan mRNA was significantly higher in the transplantation group and the blank control group compared with the degeneration control group （P 〈0.05）. Conclusions CT-guided percutaneous puncture can successfully build rabbit degenerative intervertebral disc models. Both CTGF and TIMPl-transfected cell transplantation helps to maintain disc height, and promotes the biosynthesis of tvDe II collaQen and proteoalvcan in intervertebral discs, reversinq the de（：ieneration of intervertebral discs.