Therapeutic effects of adenovirus-mediated growth and differentiation factor-5 in a mice disc degeneration model induced by annulus needle puncture

Liang, Haixiang; Ma, SF; Feng, Gang; Shen, Francis H.; Li, Xudong Joshua

doi:10.1016/j.spinee.2009.10.006

Cited by 84 publications

(74 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with previous reports, Ad-GDF-5 treatment not only promotes the expression of ECM proteins but also could improve the construction and function of NP cells in vivo via the sustained transcription and translation of ECM proteins (Wang et al, 2004;Feng et al, 2008;Liang et al, 2010).…”

Section: Discussionsupporting

confidence: 91%

“…The results not only confirmed the longterm expression of the target protein in the disc in vivo, but also highlighted the physiological improvements that occurred to the disc. Ad-GDF-5 gene therapy could restore the functions of injured discs and has the potential to be an effective treatment (Liang et al, 2010). In other research GDF-5 was transfected with mesenchymal stem cells (MSCs) by electroporation to prepare the seed cells for IVD cell therapy (Bucher et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Adenovirus-mediated GDF-5 promotes the extracellular matrix expression in degenerative nucleus pulposus cells

Luo

Liu

Zhu

et al. 2016

J. Zhejiang Univ. Sci. B

Self Cite

View full text Add to dashboard Cite

Abstract:Objective: To construct a recombinant adenovirus vector-carrying human growth and differentiation factor-5 (GDF-5) gene, investigate the biological effects of adenovirus-mediated GDF-5 (Ad-GDF-5) on extracellular matrix (ECM) expression in human degenerative disc nucleus pulposus (NP) cells, and explore a candidate gene therapy method for intervertebral disc degeneration (IDD). Methods: Human NP cells of a degenerative disc were isolated, cultured, and infected with Ad-GDF-5 using the AdEasy-1 adenovirus vector system. On Days 3, 7, 14, and 21, the contents of the sulfated glycosaminoglycan (sGAG), deoxyribonucleic acid (DNA) and hydroxyproline (Hyp), synthesis of proteoglycan and collagen II, gene expression of collagen II and aggrecan, and NP cell proliferation were assessed. Results: The adenovirus was an effective vehicle for gene delivery with prolonged expression of GDF-5. Biochemical analysis revealed increased sGAG and Hyp contents in human NP cells infected by Ad-GDF-5 whereas there was no conspicuous change in basal medium (BM) or Ad-green fluorescent protein (GFP) groups. Only cells in the Ad-GDF-5 group promoted the production of ECM, as demonstrated by the secretion of proteoglycan and up-regulation of collagen II and aggrecan at both protein and mRNA levels. The NP cell proliferation was significantly promoted. Conclusions: The data suggest that Ad-GDF-5 gene therapy is a potential treatment for IDD, which restores the functions of degenerative intervertebral disc through enhancing the ECM production of human NP cells.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Adenovirus-mediated GDF-5 promotes the extracellular matrix expression in degenerative nucleus pulposus cells

Luo

Liu

Zhu

et al. 2016

J. Zhejiang Univ. Sci. B

Self Cite

View full text Add to dashboard Cite

show abstract

“…39,40 Thus, GDF5 gene deficiency, mutation, or abnormal expression can cause variable changes in cell growth and ECM synthesis and promote the development of IDD. Increasing evidence suggests that GDF5 aids in maintaining the structural integrity of the IVD and effectively restores disc physiological function, thereby delaying or even reversing IDD.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of microRNA-34a prevents IL-1β-induced extracellular matrix degradation in nucleus pulposus by increasing GDF5 expression

Liu

Zhang

Feng

et al. 2016

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

Accumulating evidence indicates that miRNAs, a class of small non-coding RNAs, are implicated in the pathogenesis of various diseases such as cancer and intervertebral disc degeneration. The aim of this study was to investigate the expression and the biological function of microRNA-34a in intervertebral disc degeneration. In this study, microRNA-34a expression was assessed in nucleus pulposus specimens and in IL-1b-stimulated nucleus pulposus cells by real-time polymerase chain reaction. microRNA34a functions were investigated by using gain and loss of function experiments in nucleus pulposus cells and a dual luciferase reporter assay in 293T cells. microRNA-34a was dramatically up-regulated in degenerative nucleus pulposus tissues and in IL-1b-stimulated nucleus pulposus cells when compared with controls. Furthermore, growth differentiation factor 5 was identified as a target of microRNA-34a. Aberrant expression of microRNA-34a inhibited growth differentiation factor 5 expression by direct binding to its 3 0 -untranslated region. This inhibition was abolished by mutation of the microRNA-34a binding sites. In addition, microRNA-34a silencing reversed IL-1b-induced decrease in type II collagen and aggrecan expression in nucleus pulposus cells. This effect was substantially suppressed by growth differentiation factor 5 silencing. Our results suggested that microRNA-34a inhibition prevents IL-1b-induced extracellular matrix degradation in human nucleus pulposus by increasing growth differentiation factor 5 expression. microRNA-34a inhibition may be a novel molecular target for intervertebral disc degeneration treatment through the prevention of nucleus pulposus extracellular matrix degradation.

show abstract

“…GDF5 protein treatment augmented anabolic metabolism of disc cells from either GDF5 deficient mice or wild-type mice. Intra-disc injection experiments also showed that the administration of GDF5 promotes inner AF cells migrating to injured NP area and presenting chondrogenic phenotype [81].…”

Section: Af Cells Response To Different Stimulimentioning

confidence: 93%

The challenge and advancement of annulus fibrosus tissue engineering

Jin

Shimmer

2013

Eur Spine J

View full text Add to dashboard Cite

Background Intervertebral disc degeneration, a main cause of back pain, is an endemic problem and a big economic burden for the health care system. Current treatments are symptom relieving but do not address underlying problems-biological and structural deterioration of the disc. Tissue engineering is an emerging approach for the treatment of intervertebral disc degeneration since it restores the functionality of native tissues. Although numerous studies have focused on the nucleus pulposus tissue engineering and achieved successes in laboratory settings, disc tissue engineering without annulus fibrosus for the end stage of disc degeneration is deemed to fail. The purpose of this article is to review the advancement of annulus fibrosus tissue engineering. Material and Methods Relevant articles regarding annulus fibrosus tissue engineering were identified in PubMed and Medline databases. Results The ideal strategy for disc regeneration is to restore the function and integrity of the disc by using biomaterials, native matrices, growth factors, and cells that producing matrices. In the past decades there are tremendous advancement in annulus fibrosus tissue engineering including cell biology, biomaterials, and whole disc replacement. The recent promising results on whole disc tissue engineering-a composite of annulus fibrosus and nucleus pulposus-make the tissue engineering approach more appealing.Conclusion Despite the promising results in disc tissue engineering, there is still much work to be done regarding the clinical application.

show abstract

Therapeutic effects of adenovirus-mediated growth and differentiation factor-5 in a mice disc degeneration model induced by annulus needle puncture

Cited by 84 publications

References 40 publications

Adenovirus-mediated GDF-5 promotes the extracellular matrix expression in degenerative nucleus pulposus cells

Adenovirus-mediated GDF-5 promotes the extracellular matrix expression in degenerative nucleus pulposus cells

Inhibition of microRNA-34a prevents IL-1β-induced extracellular matrix degradation in nucleus pulposus by increasing GDF5 expression

The challenge and advancement of annulus fibrosus tissue engineering

Contact Info

Product

Resources

About